The National Research Council's assessment of research doctorate programs can be used to strengthen doctoral programs in nutrition.

The National Research Council (NRC) is for the first time including the field of nutrition in its Assessment of Research Doctorate Programs in 2006. This assessment will rate doctoral programs, in terms of research impact and graduate student support and outcomes, through the use of questionnaires and standardized national databases (such as research funding, publications, and citations of publications) rather than through name recognition as was used in past NRC surveys of graduate programs. Nutritionists can make this survey more valuable to the field by making sure all eligible faculty involved in training of graduate students in nutrition are included in the survey, by encouraging all eligible faculty members to complete the faculty questionnaire, and by being prepared to use and discuss the data and reports when they are released in 2007. The nutrition community should use the data from this national survey to strengthen doctoral programs and research in nutrition.

Dietary supplement use: consumer characteristics and interests.

Four major issues should be considered in a discussion of what consumers need to know about supplements and herbal treatments. 1) Usage of supplements is changing as consumers are taking charge of their health and seeking alternative forms of medicine (Eisenberg et al. 1998, Gilbert 1999 ). 2) The characteristics of supplement users have been profiled in numerous academic and industrial surveys. However, even the best models based on consumers' characteristics can predict < 30% of diet-related behavior (Baranowski et al. 1999 ). 3) Experts in traditional medicine and nutrition lack information on supplements and herbals. The Practice and Policy Guidelines Panel of the National Institute of Health Office of Alternative Medicine (1997) stated that practices used in complementary and alternative medicine were "unsuitable for the development of evidence-based practice guidelines." Well-designed basic and clinical research is needed on the efficacy, bioavailability and safety of supplements and herbal medications. 4) It is debatable which agencies and professionals are the best gatekeepers of information on supplements and herbals. Significant numbers of consumers do not seem to rely on their physicians for information on alternative forms of medicine (Eisenberg 1997 ). Despite the obstacles, the traditional medical community (including nutritionists) should focus more research efforts on diet supplements and herbal treatments and increase training on these topics for students majoring in health care fields. Then health care professionals can mount high quality, targeted education programs for consumers.

Nutrition versus toxicology of manganese in humans: evaluation of potential biomarkers.

Manganese intake can vary greatly with food choices, water composition, and supplement use. Thus, individuals consuming Western diets consume from < 1 to > 10 mg Mn/d. The levels of manganese intake associated with adverse effects (both deficient and toxic) are debatable. Moreover, many of the symptoms of manganese deficiency (growth retardation, changes in circulating HDL cholesterol and glucose levels, reproductive failure) and manganese toxicity (growth depression, anemia) are non-specific. The bone deformities observed in manganese-deficient animals and neurological symptoms of individuals who have inhaled excess manganese are permanent and illustrate the need to identify sensitive biomarkers of manganese status that appear before these symptoms. Manganese balance and excretion data are not useful biomarkers of manganese exposure but demonstrate that the body is protected against manganese toxicity primarily by low absorption and/or rapid presystemic elimination of manganese by the liver. Serum manganese concentrations in combination with lymphocyte manganese-dependent superoxide dismutase (MnSOD) activity and perhaps blood arginase activity, appear to be the best ways to monitor ingestion of insufficient manganese. Serum manganese concentrations in combination with brain MRI (magnetic resonance imaging) scans, and perhaps a battery of neurofunctional tests, appear to be the best ways to monitor excessive exposure to manganese.

Nondigestible carbohydrates and mineral bioavailability.

Generally, fiber and compounds associated with fiber in cereal products (e.g., phytates) have been found to reduce the apparent absorption of minerals (such as calcium, magnesium, zinc and manganese) in humans, livestock and animal models. The effects of "soluble" forms of fiber (specifically pectins, gums, resistant starches, lactulose, oligofructose and inulin) on mineral absorption are more difficult to characterize. The addition of these soluble forms of fiber has been found in various studies to add viscosity to the gut contents, promote fermentation and the production of volatile fatty acids in the cecum, have a trophic effect on the ceca of animals and increase serum enteroglucagon concentrations. Thus it is not surprising that the addition of soluble forms of fiber to diets often has been found to improve absorption of minerals. This may reflect absorption of electrolytes from the large intestine. Future work should address the mechanisms by which ingestion of nondigestible carbohydrates improves mineral absorption in humans.

Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study.

The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.

Serum carotenoids and tocopherols and incidence of age-related nuclear cataract.

BACKGROUND: It is not known whether the protective effects of antioxidants on cataract observed in experimental animals are relevant to age-related opacities in humans. OBJECTIVE: The relations of serum carotenoids and tocopherols to the incidence of age-related nuclear cataract were investigated in a random sample of 400 adults, 50-86 y of age, in the Beaver Dam Eye Study. DESIGN: Nuclear opacity was assessed by using lens photographs taken at baseline (in 1988-1990) and follow-up (in 1993-1995). Nonfasting concentrations of individual carotenoids and alpha- and gamma-tocopherol, were determined from serum obtained at baseline. A total of 252 persons were eligible for incident cataract, of whom 57 developed nuclear cataract in at least one eye. Results were adjusted for age, smoking, serum cholesterol, heavy drinking, adiposity, and, in the tocopherol models, dietary linoleic acid intake. RESULTS: Only serum tocopherol (the sum of alpha- and gamma-tocopherol, in micromol/mmol cholesterol) was associated with cataract. For total serum tocopherol, persons in tertile 3 had a lower risk of cataract than persons in tertile 1 [odds ratio (OR): 0.4; 95% CI: 0.2, 0.9; P = 0.03 for linear trend]. Although serum carotenoids were not significantly associated with nuclear cataract, marginal inverse associations with lutein (OR: 0.3; 95% CI: 0.1, 1.2; P = 0.13 for linear trend) and cryptoxanthin (OR: 0.3; 95% CI: 0.1, 1.3; P = 0.11 for linear trend) were suggested in people < or = 65 y of age. CONCLUSIONS: Findings were compatible with the possibility that nuclear cataract may be linked inversely to vitamin E status, but neither strongly supported nor negated the hypothesized inverse association of nuclear cataract with serum carotenoids.

Supplement users differ from nonusers in demographic, lifestyle, dietary and health characteristics.

This study delineates demographic, lifestyle, dietary and health factors associated with the use of supplements at varying levels. Data are from a population-based cohort of 2,152 middle- to older-age adults living in Beaver Dam, Wisconsin. Information was collected by in-person interviews between 1988-1990. Associations were adjusted for gender and age. Use of supplements was more prevalent among women, persons with more than 12 years of education, those with relatively low body mass indices, persons with active lifestyles, and persons who never smoked as compared to current smokers (P

Effect of the size of an oral dose of aluminium on the relative importance of biliary v. urinary aluminium excretion in conscious rats.

We compared biliary and urinary aluminium (Al) excretion following ingestion of dietary or gavage dosing of low to moderate pharmacological doses of aluminium. Bile was collected from 26 conscious, male Sprague Dawley rats following administration of a single gavage dose of 0, 0.25, 0.5 or 1 mmol Al/kg body weight in 1 ml 16% citrate solution (equivalent to 0-650 mg Al to a 70-kg human). Urine was collected from 20 additional rats following similar dosing. Biliary Al secretion rates were highest in the first hour after dosing. Cumulatively, rats given 0.5 or 1 mmol Al/kg body weight excreted significantly more Al in bile than rats dosed with 0.25 mmol Al/kg body weight, which excreted more Al bile than control rats. Urinary Al excretion was many-fold higher than biliary Al excretion by rats dosed with Al but was less than biliary Al excretion by control rats exposed to dietary Al only. These results suggest that the liver was capable of secreting small amounts of absorbed dietary Al into bile but that the kidneys became the primary excretory organs for Al when the liver's secretory capacity was surpassed after ingestion of pharmacological doses of Al.

Kinetics of aluminum disposition after ingestion of low to moderate pharmacological doses of aluminum.

We assessed the kinetics of aluminum uptake and elimination by tissues of Sprague Dawley rats following a single gavage dose of 0, 0.25, 0.5, or 1 mmol Al/kg body weight (b.w.) in 1 ml of 16% citrate (equivalent to 0-650 mg Al to a 70-kg human). Serum, liver, kidney, and tibia aluminum concentrations were measured 15, 30, 60, 120, 270, and 360 min after dosing. Serum aluminum concentrations were proportional to dose in rats dosed with 0.25 or 0.5 mmol Al/kg b.w. but were not proportional to dose for rats dosed with 1 mmol Al/kg b.w. Elimination half-lives of serum aluminum were similar for all treatments (102-119 min) which suggests that the non-linear aluminum kinetics in serum reflected a difference in absorption of the highest dose. Although fasted rats dosed with 0.25 or 1 mmol Al/kg b.w. with citrate absorbed aluminum with similar efficiency (4.2% of dose), the length of the absorptive period was prolonged in the rats given the highest does. Total absorbed aluminum mass in rats dosed with 0.25 and 0.5 mmol vs. 1 mmol Al/kg b.w. reached a plateau at 120 vs. 270 min after dosing, respectively. The kinetics of aluminum in liver, bone, and kidney were generally dose-independent. Elimination half-lives of liver aluminum were similar for all aluminum treatments (267-465 min); elimination half-lives could not be estimated in bone and kidney because of turnover exceeded the 6 h collection period.

Dietary standards for manganese: overlap between nutritional and toxicological studies.

The Estimated Safe and Adequate Daily Dietary Intake (ESADDI) for adults for manganese is 2-5 mg Mn/d. The LOAEL (lowest-observable-adverse-effect level) for manganese in water is 0.06 mg Mn/(kg.d) or 4.2 mg Mn/d for a 70-kg individual. The inconsistency in these standards reflects limitations in the available data as well as differences in the way in which the standards are calculated. Manganese balance and excretion data are not useful biomarkers of manganese exposure but do demonstrate that the body is protected against manganese toxicity primarily by low absorption and/or rapid presystemic elimination of manganese by the liver. Serum manganese concentrations in combination with lymphocyte manganese-dependent superoxide dismutase (MnSOD) activity, and perhaps blood arginase activity, seem to be the best way to monitor ingestion of insufficient manganese. Serum manganese concentrations in combination with brain magnetic resonance imaging (MRI) scans, and perhaps a battery of neurofunctional tests, seem to be the best way to monitor excessive exposure to manganese.

Aluminum exposure and metabolism.

Aluminum (Al) is a nonessential, toxic metal to which humans are frequently exposed. Oral exposure to aluminum occurs through ingestion of aluminum-containing pharmaceuticals and to a lesser extent foods and water. Parenteral exposure to aluminum can occur via contaminated total parenteral nutrition (TPN), intravenous (i.v.) solutions, or contaminated dialysates. Inhalation exposure may be important in some occupational settings. The gut is the most effective organ in preventing tissue aluminum accumulation after oral exposure. Typically gastrointestinal absorption of aluminum from diets is < 1%. Although the mechanisms of aluminum absorption have not been elucidated, both passive and active transcellular processes and paracellular transport are believed to occur. Aluminum and calcium may share some absorptive pathways. Aluminum absorption is also affected by the speciation of aluminum and a variety of other substances, including citrate, in the gut milieu. Not all absorbed or parenterally delivered aluminum is excreted in urine. Low glomerular filtration of aluminum reflects that most aluminum in plasma is nonfiltrable because of complexation to proteins, predominantly transferrin. The importance of biliary secretion of aluminum is debatable and the mechanism(s) is poorly understood and appears to be saturable by fairly low oral doses of aluminum.

Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney.

Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.

Association of zinc and antioxidant nutrients with age-related maculopathy.

OBJECTIVE: To quantify relationships between dietary intake of zinc and antioxidant nutrients and early and late age-related maculopathy (ARM). DESIGN: A retrospective longitudinal cohort design using data pertaining to diets in the past (1978-1980), which were assessed retrospectively using a food frequency questionnaire. SETTING: Beaver Dam, Wis. PATIENTS: A 50% random sample of free-living Beaver Dam Eye Study participants, 43 to 86 years of age (N = 1968). MAIN OUTCOME MEASURE: The presence of early and late ARM determined from fundus photography. RESULTS: People in the highest vs lowest quintiles for intake of zinc from foods had lower risk for early ARM (odds ratio = 0.6, 95% confidence interval, 0.4-1.0, P for trend < .05). This relationship appeared to be stronger for some types of early ARM (increased retinal pigment) than for others. Zinc intake was unrelated to late ARM. However, small numbers (n = 30) of people with this condition limit the ability to draw conclusions about this later stage. Levels of carotenoids were unrelated to early or late ARM. Odds for early ARM were lower in people in the highest vs lowest quintiles for the intake of vitamins C or E. However, these associations were not statistically significant. CONCLUSIONS: The data are weakly supportive of a protective effect of zinc on the development of some forms of early ARM. Prospective studies are needed to further evaluate the potential influence of these and other nutritional factors on different types and stages of age-related macular degeneration.

Bile is an important route of elimination of ingested aluminum by conscious male Sprague-Dawley rats.

We assessed the importance of bile as an excretory route for ingested aluminum (AI). Bile dusts in 30 male Sprague-Dawley rats were cannulated to allow both bile collection and reinfusion of bile acids. Five days after surgery, rats (average weight = 191 +/- 4 g) were given a single oral dose of aluminum (0, 0.2, 0.4, or 0.8 mmol) as aluminum lactate in 1 ml of 16% citrate by gavage. Bile was collected 1-7 h after dosing from unanesthetized rats. Biliary aluminum secretion was highest during the first hour of bile collection. All rats dosed with aluminum secreted significantly greater amounts of aluminum in bile than control rats. However, biliary aluminum secretion did not vary among animals given the different aluminum doses suggesting that biliary secretion of aluminum was saturated at these doses. Rats dosed with 0.8 mmol A1 retained significantly greater amounts of aluminum in soft tissues than those given 0.2 or 0.4 mmol A1. This result suggests that physiological were unable to prevent tissue aluminum accumulation in the rats given the highest dose.

Biliary manganese excretion in conscious rats is affected by acute and chronic manganese intake but not by dietary fat.

We hypothesized that biliary excretion of manganese would be sensitive to acute and chronic variations in manganese and fat intakes. In the acute study, we gavaged rats with solutions containing 54Mn with either 0, 0.2, 1 or 10 mg Mn as MnCl2. We collected bile from unanesthesized rats that were simultaneously reinfused with bile acids. Total manganese excretion (from 0.5 to 6.5 h after dosing) was proportional to the acute doses (approximately 3.4% of doses). In the chronic study, weanling rats were fed diets containing 5 or 20 g corn oil/g diet and 0.49 or 72 micrograms Mn/g diet for 8 wk and then deprived of food for 12 h before bile collection. Manganese-deficient animals excreted only 0.7% as much manganese in bile as manganese-replete animals, but this reduction was not sufficient to prevent 50-80% reduction of tissue manganese concentrations. Moreover, biliary manganese excretion (calculated for 24 h) by both manganese-deficient and manganese-replete rats (deprived of food for previous 12 h) accounted for only 1% of their manganese intake on the previous day. Dietary fat and manganese concentrations had few effects on excretion of total or individual bile acids. Ours is the first report of biliary excretion of orally administered manganese by conscious rats.

Manganese protects against heart mitochondrial lipid peroxidation in rats fed high levels of polyunsaturated fatty acids.

We demonstrated previously that dietary manganese (Mn) deficiency depressed Mn concentrations in most tissues and consistently depressed Mn superoxide dismutase (MnSOD) levels in heart. To examine the functional consequences of these effects, we fed weanling male Sprague-Dawley rats (n = 12/diet) diets containing 20% (wt/wt) corn oil or 19% menhaden oil + 1% corn oil by weight and 0.75 or 82 mg Mn/kg diet for 2 mo (the fish oil mixture was supplemented with (+)-(mixed)-alpha-tocopherol to the level in corn oil). Heart and liver Mn concentrations in the Mn-deficient rats were 56% of those in Mn-adequate rats (P < 0.0001), confirming Mn deficiency. The Mn-deficient rats had more conjugated dienes in heart mitochondria than Mn-adequate rats (P < 0.001); rats fed fish oil had more conjugated dienes than those fed corn oil (P < 0.001). The MnSOD activity was inversely correlated with conjugated dienes (r = -0.71, P < 0.005), and Mn-deficient rats had 37% less MnSOD activity in the heart than did Mn-adequate rats (P < 0.0001). The dietary treatments did not affect heart microsomal conjugated diene formation, possibly because of compensation by copper-zinc (CuZn) SOD activity; CuZnSOD activities were 35% greater in the hearts of Mn-deficient animals (P < 0.01). Liver was less sensitive to Mn deficiency than was the heart as judged by MnSOD activity and conjugated diene formation. This work is the first to demonstrate that dietary Mn protects against in vivo oxidation of heart mitochondrial membranes.