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Biomedical subjects

R A Jacob

Publications and source records attributed to R A Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1995

In vivo methylation capacity is not impaired in healthy men during short-term dietary folate and methyl group restriction.

Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on in vivo methylation capability. The men were housed in a metabolic unit for the entire 108 d of the study. After a 9-d baseline period (Period 1), the men were fed a soy-product-amino acid defined diet for 45 d, which provided 25 micrograms/d of folate for 30 d (Period 2) and, with a folate supplement, 99 micrograms/d for 15 d (Period 3). During Period 2 and Period 3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (Periods 4-6), with a crossover of methionine intakes in Period 5 and Period 6. A 1-g oral dose of nicotinamide was given at the end of each period and methylated urine metabolites determined. Other measures related to in vivo methylation capability included urine creatinine, and plasma and urine carnitine. Even with moderate folate depletion, none of these measures was decreased by low methionine and choline intakes. Plasma methionine concentrations were unchanged throughout. Limiting exogenous methyl group intake by restricting dietary methionine and choline did not impair in vivo methylation capabilities for the variables tested, even at low folate intake.

Administration, Oral↗
PubMed1994

Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction.

Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on folate requirement and status. The men were housed in a metabolic unit for the entire 108-d study. After a 9-d base-line period (P1), the men were fed an amino acid-defined soybean product diet for 45 d, which provided 25 micrograms/d of folate for 30 d (P2) and (with a folate supplement) 99 micrograms/d for 15 d (P3). During P2 and P3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (P4-P6), with a cross-over of methionine intakes in P5 and P6. Restricting dietary methyl group intake did not increase the dietary folate requirement. Plasma total homocysteine rose during folate depletion and correlated inversely with plasma folate; however, the response of homocysteine to changes in folate intake varied among individuals from very strong to absent. The results support previous suggestions that increased plasma homocysteine concentrations provide a marker of functional folate deficiency, and further indicate that individuals may differ greatly in their susceptibility to hyperhomocysteinemia due to low folate intakes. Judged by the lack of normalization of high homocysteine concentrations during folate repletion, the current folate RDA for adult men may not provide the expected margin of protection.

Adult↗
PubMed1993

Biochemical assessment of vitamins and trace metals.

The choice of nutritional assessment tests must be made with care, as the available tests may reflect recent dietary intakes or body tissue stores to different degrees. The interpretation of nutritional assessment tests is complicated by the dynamic nature and broad range of nutrient intake and metabolism and by a relative lack of age- and sex-specific reference ranges. The latter problem can be minimized by the use of function-based methods, such as the measurement of vitamin-dependent red cell enzyme activities to assess B vitamin status; however, few suitable function-based methods are now available, and more research in this area is needed. Because calibration standards and quality control materials may not be readily available, laboratory analysts planning nutritional assessment testing must be especially careful in establishing the credibility of assays and the quality control program. Recent advances in analytic methodology include the specificity offered by HPLC techniques and methodologies that provide simultaneous determination of more than one nutrient (or form of nutrient) in a single procedure. Examples of the latter include HPLC methods that provide B vitamin or fat-soluble vitamin profiles, and emission spectrometry techniques that provide trace metal profiles. Further work in providing useful nutritional assessment profiles and convenient automated methods is needed.

Humans↗
PubMed1992

Plasma carotenoid levels in human subjects fed a low carotenoid diet.

The purpose of this study was to investigate the effect of a low carotenoid diet on plasma carotenoid levels in humans. Twelve healthy male subjects were fed a low carotenoid diet under controlled conditions for 13 wk in a live-in metabolic unit, as part of a study of vitamin C requirement. Plasma carotenoids (zeaxanthin/lutein, cryptoxanthin, lycopene, alpha-carotene, beta-carotene) were measured with HPLC on study days 2-3, 14-15, 35-36 and 63-64. The rate of decline was rapid between d 2-3 and d 14-15, when the concentration of each carotenoid decreased significantly (P less than 0.05). Although accurate figures for half-life are not possible without more frequent sampling points, mean plasma depletion half-life seemed to be less than 12 d for beta-carotene, alpha-carotene and cryptoxanthin, between 12 and 33 d for lycopene and between 33 and 61 d for zeaxanthin/lutein. Because the decline was not linear over the study period, these data suggest the possibility of at least two body pools of these compounds, with one pool having a more rapid turnover rate. Because there is a significant decline in plasma carotenoid levels within the first 2 wk of a low carotenoid diet, determination of levels of these compounds may be useful only in the assessment of short-term intake.

Ascorbic Acid↗
PubMed1992

Cellular ascorbate depletion in healthy men.

To clarify the relationship of plasma ascorbic acid to cellular ascorbic acid levels, we determined plasma, lymphocyte, buccal cell and semen ascorbic acid in eight healthy men consuming controlled ascorbic acid intakes of 5, 10, 20, 60 or 250 mg/d over 13 wk while living in a metabolic unit. Levels of ascorbic acid in all four specimen types were significantly lower during the three lowest intakes (5, 10, or 20 mg/d) compared with the 60 or 250 mg/d intakes, but only plasma and lymphocyte ascorbic acid levels discriminated between these intakes unequivocally and with no overlap. Priority for maintenance of intracellular lymphocyte ascorbic acid was indicated by rapid repletion of lymphocytes compared with plasma and semen at 60 mg/d intake. Strong correlations of plasma with lymphocyte ascorbic acid within individuals indicated that plasma levels would reliably reflect low lymphocyte levels in nutrition monitoring surveys. Buccal cell ascorbic acid may be useful as a noninvasive screening test for ascorbic acid deficiency. Semen and sperm qualities were unchanged despite an average decline in semen ascorbic acid to 24% of baseline. Short-term ascorbic acid depletion in healthy men did not adversely affect sperm qualities related to fertility nor did moderate supplementation improve them.

Adult↗
PubMed1991

Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.

Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Immunocompetence and oxidant defense during ascorbate depletion of healthy men.

To determine nonscorbutic effects of moderate vitamin C deficiency we measured immune function and oxidative damage in eight healthy men (25-43 y) who consumed 5-250 mg/d of ascorbic acid over 92 d on a metabolic unit. During ascorbic acid intakes of 5, 10, or 20 mg/d, subjects attained a state of moderate ascorbic acid deficiency as ascorbic acid concentrations in plasma, leucocytes, semen, and buccal cells dropped to less than 50% of baseline with no scorbutic symptoms observed. No changes in cell proliferation, erythrocyte antioxidant enzymes, and DNA strand breaks were observed; however, blood levels of glutathione and NAD(P) decreased during ascorbic acid deficiency, as did delayed hypersensitivity responsiveness. Concentrations of the oxidatively modified DNA base, 8-hydroxydeoxyguanosine in sperm DNA and fecapentaenes, ubiquitous fecal mutagens, were increased during ascorbic acid depletion. Moderate vitamin C deficiency, in the absence of scurvy, results in alteration of antioxidant chemistries and may permit increased oxidative damage.

Adult↗
PubMed1991

Glutathione blood levels and other oxidant defense indices in men fed diets low in vitamin C.

Because ascorbic acid is an important contributor to the oxidant defense system in body tissues, we studied the effects of a low dietary intake of ascorbic acid on various indicators of oxidant defense and oxidant damage. During a 13-wk study eight healthy men (25-43 y), residing in a live-in metabolic unit, were fed controlled diets containing different amounts of ascorbic acid for four consecutive periods: period 1 = 250 mg/d for 4 d; period 2 = 5 mg/d for 32 d; period 3 = 10 or 20 mg/d for 28 d and period 4 = 60 or 250 mg/d for 28 d. Measurements were made at several time intervals of the activities of glutathione peroxidase and superoxide dismutase in RBC, DNA strand breaks in mononuclear leucocytes, glutathione concentrations in plasma and RBC and NAD and NADP in RBC. After 60 d of low ascorbic acid intakes and associated with plasma ascorbic acid levels less than 6 mumol/L, the total glutathione concentration and the reduced glutathione:oxidized glutathione ratio were decreased in plasma. At the same time NAD and NADP levels in RBC were elevated. It seems that chronic marginal vitamin C deficiency states may be associated with selected biochemical changes in oxidant defense indices.

Adult↗
PubMed1991

Effects of ascorbic acid depletion and supplementation on periodontal health and subgingival microflora in humans.

This study describes the relationship between varying ascorbate intake, periodontal status, and subgingival microflora as part of a multidisciplinary investigation of ascorbic acid (AA) metabolism in young men housed for 13 weeks in a nutrition suite that provided controlled periods of ascorbic acid depletion and repletion. Twelve medically healthy non-smoking men, aged 25 to 43 years, ate a rotating four-day diet adequate in all nutrients except ascorbic acid. Following an initial baseline period during which the subjects received 250 mg AA/day, the subjects received 5 mg AA/day for a 32-day depletion period. Eight of the 12 subjects participated in a subsequent 56-day repletion period designed to replace the reduced body AA pool slowly. Plasma and leukocyte ascorbate levels, Plaque Index, Gingival Index, probing depths, and attachment level were monitored at the beginning and end of the depletion and repletion periods. Subgingival plaque samples were obtained and examined for selected organisms by indirect immunofluorescence microscopy. A uniform oral hygiene program was reinforced after each examination. Ascorbate concentrations in plasma and leukocytes responded rapidly to changes in vitamin C intake. There were no significant changes in plaque accumulation, probing pocket depth, or attachment level during the study. In contrast, gingival bleeding increased significantly after the period of AA depletion and returned to baseline values after the period of AA repletion. However, no relationship could be demonstrated between either the presence or proportion of target periodontal micro-organisms and measures of bleeding or ascorbate levels.

Actinomyces viscosus↗
PubMed1990

Urinary hydroxyproline excretion and vitamin C status in healthy young men.

The relationship between ascorbic acid status and the urinary excretion of hydroxyproline was examined in 11 healthy male subjects fed an ascorbic acid-deficient diet for 14 wk while in a metabolic unit. The diet provided 5 mg ascorbic acid/d and was supplemented with ascorbic acid to give intakes of 65 mg/d (2 wk), 5 mg/d (4 wk), 605 mg/d (3 wk), 5 mg/d (4 wk), and an average 375 mg/d (1 wk). The urinary excretion of hydroxyproline increased by an average of 16% and 30% after the first and second depletion periods, respectively, and decreased to baseline values after supplementation with normal or high doses of vitamin C. Significant (p less than 0.05) inverse correlations were found between urinary hydroxyproline and plasma, red cell, and leukocyte ascorbic acid. These results show that urinary hydroxyproline excretion increases during human vitamin C deficiency but that this effect is not strong enough to provide a reliable marker of mild vitamin C deficiency.

Adult↗
PubMed1990

Assessment of human vitamin C status.

Since no reliable functional markers of human vitamin C status have been demonstrated, determination of vitamin C levels in blood plasma and/or leukocytes remains the current choice for individual and population assessments. Newer analytical techniques, especially high-performance liquid chromatography, allow determination of reduced (ascorbic acid), oxidized (dehydroascorbic acid), or total amounts of vitamin C in biological specimens or foods. Plasma levels of vitamin C forms are easily determined but may not reflect tissue content as well as leukocyte levels. The vitamin C content of leukocyte cell types varies severalfold and, unlike plasma, leukocytes may contain an appreciable fraction of dehydroascorbic acid. The effects of sex, age, cigarette smoking, drugs, and physiological factors on vitamin C levels are better known for plasma than leukocytes. To realize the potential of leukocytes as measures of vitamin C status, continued work is needed in standardizing the methodology and interpretive guidelines and simplifying the technique for blood processing. The search for specific functional markers of vitamin C deficiency should continue. Candidate markers may involve pathways of carnitine or collagen metabolism, immunocompetence, or antioxidant defense.

Ascorbic Acid↗
PubMed1990

The prevalence of cardiovascular risk factors among elderly Chinese Americans.

In 1981 to 1983, the nutrition and health status of 346 Chinese immigrants in Boston, Mass, aged 60 to 96 years was surveyed and analyzed for cardiovascular risk factors. These elderly Chinese were physically active and seldom obese and consumed a high-carbohydrate (57% of total energy intake), low-fat (24% of total energy intake), low-ascorbic acid (0.62 mmol/d) diet. Current cigarette smoking was common (39%) only in men, while alcoholism was rare in both sexes. Compared with elderly whites, they had lower mean blood pressure and blood levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol, apolipoproteins A-I and B, and ascorbic acid. These characteristics resemble those of the urban population in mainland China, where hemorrhagic stroke is the major cause of cardiovascular mortality.

Aged↗
PubMed1989

Ascorbic acid, HDL cholesterol, and apolipoprotein A-I in an elderly Chinese population in Boston.

The relationships between plasma HDL cholesterol, apolipoprotein A-I, and plasma ascorbic acid were examined in 146 women and 92 men in a Chinese population in Boston, aged 60 and above. A significant partial correlation (r = 0.21, p = 0.015) between plasma ascorbic acid and plasma HDL cholesterol was observed among (predominantly nonsmoking) females after the effects of potentially confounding variables were taken into account. A similar relationship among 26 nonsmoking men was suggestive but inconclusive; there was no evidence of a relationship among 66 male smokers. The partial correlation between plasma apolipoprotein A-I and plasma ascorbic acid was marginally significant for women (r = 0.22, p = 0.057, n = 87) but was highly significant for men (r = 0.43, p = 0.007, n = 51). The correlation coefficient for men was highly dependent on smoking status, being 0.80 for those who never smoked and almost zero for current smokers.

Aged↗
PubMed1989

Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users.

We studied the relationships of supplemental and total vitamin A and supplemental vitamin E intake with fasting plasma biochemical indicators of vitamin A and vitamin E nutritional status among 562 healthy elderly people (aged 60-98 y) and 194 healthy young adult (aged 19-59 y) volunteers. All subjects were nonsmokers. For the young adults, plasma retinol was significantly greater in males than in females (p less than 0.01); retinol was not related to supplemental vitamin A intake for either group. Fasting plasma retinyl esters demonstrated a significant increase with vitamin A supplement use. For supplemental vitamin A intakes of 5001-10,000 IU/d, a 2.5-fold increase over nonusers in fasting plasma retinyl esters was observed for elderly people (p less than 0.05) and a 1.5-fold increase for young adults (p greater than 0.20). For elderly people, greater fasting plasma retinyl esters were associated with long-term vitamin A supplement use (greater than 5 y) and biochemical evidence of liver damage. Elderly people who take vitamin A supplements may be at increased risk for vitamin A overload.

Aged↗
PubMed1989

Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan.

Seven male subjects housed in a controlled metabolic unit for 80 d were fed diets containing amounts of niacin and tryptophan ranging from 6.1 to 32 niacin equivalents (NE) per day. Erythrocyte nicotinamide adenine dinucleotide (NAD) and nicotinamide nucleotide phosphate (NADP), activity of nicotinic acid mononucleotide phosphoribosyltransferase (NMNPRT), plasma tryptophan levels and the urinary excretion of organic acids were measured during dietary periods of low (6.1 or 10.1), adequate (19) and high (25 or 32) NE intake. With both low NE diets, NAD levels in erythrocytes decreased by approximately 70% and increased during repletion with an adequate NE diet. NADP levels remained relatively unchanged. Plasma tryptophan levels decreased by 40% and 10% in subjects ingesting diets of 6.1 and 10.1 NE/d, respectively. A daily 7.8-g leucine supplement during repletion was not associated with changes in plasma tryptophan levels or erythrocyte NAD and NADP levels at the end of the period. No changes in NMNPRT activity or organic acid excretion were found during the study. The results indicate that the erythrocyte NAD level may serve as a sensitive indicator for the assessment of niacin status. Also, a niacin index, the ratio of erythrocyte NAD to NADP, below 1.0 may identify subjects at risk of developing a niacin deficiency.

Adult↗