Howerde E. Sauberlich

High risk of HIV-related mortality is associated with selenium deficiency

To determine the independent contribution of specific immunologic and nutritional factors on survival in HIV-1 disease, CD4 cell count, antiretroviral treatment, plasma levels of vitamins A, E, B6, and B12 and minerals selenium and zinc were considered in relation to relative risk for HIV-related mortality. Immune parameters and nutrients known to affect immune function were evaluated at 6-month intervals in 125 HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5 years. A total of 21 of the HIV-1-infected participants died of HIV-related causes during the 3.5-year longitudinal study. Subclinical malnutrition (i.e., overly low levels of prealbumin, relative risk [RR] = 4.01, p < 0.007), deficiency of vitamin A (RR = 3.23, p < 0.03), vitamin B12 deficiency (RR = 8.33, p < 0.009), zinc deficiency (RR = 2.29.1, p < 0.04), and selenium deficiency (RR = 19.9, p < 0.0001) over time, but not zidovudine treatment, were shown to each be associated with HIV-1-related mortality independent of CD4 cell counts <200/mm3 at baseline, and CD4 counts over time. When all factors that could affect survival, including CD4 counts <200/mm3 at baseline, CD4 levels over time, and nutrient deficiencies were considered jointly, only CD4 counts over time (RR = 0.69, p < 0.04) and selenium deficiency (RR = 10.8, p < 0.002) were significantly associated with mortality. These results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1 infection.

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

ObjectiveTo determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DesignA longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SettingThe study was performed on an outpatient basis at the University of Miami School of Medicine. ParticipantsOne hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. Main outcome measuresBiochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. ResultsDespite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. ConclusionSpecific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

Micronutrients and HIV-1 disease progression

ObjectiveTo determine whether nutritional status affects immunological markers of HIV-1 disease progression. DesignA longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with β2-microglobulin (β2M; AIDS index) over an 18-month follow-up. MethodsBicohemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B,, B2/ Be, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and β2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. ResultsDevelopment of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P= 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P= 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by ziddvudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P= 0.041) and the AIDS index (P= 0.005). ConclusionsThese data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Oral folic acid supplementation for cervical dysplasia: A clinical intervention trial

OBJECTIVE We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.

HIV-1 infection in women is associated with severe nutritional deficiencies

Nutritional deficiencies may contribute to immune dysregulation, and have been shown to be sensitive markers of HIV-1 disease progression. Only limited information exists, however, regarding the nutritional profile of HIV-1-seropositive drug abusers. Immune and nutritional measurements were obtained in a subsample of 125 subjects from a larger cohort of drug users being followed for HIV-1 infection and cofactors of disease progression. Nutritional deficiencies, particularly vitamins A, E, and zinc, were widespread with up to 86% of the drug users exhibiting at least one nutritional alteration. Although immune parameters (CD4 count, CD8 count, beta2-microglobulin) were similar in the HIV-1-infected men and women, women had significantly poorer overall nutritional status, as measured by plasma proteins, which are considered to be sensitive markers of malnutrition. A comparison of individuals with advanced disease (CD4 count <200/mm3) revealed significantly lower levels of plasma prealbumin (p < .01), selenium, (p < .05), and greater deficiency of vitamins A (p < .01) and E (p < .05) in women than in men. The greater severity of nutritional deficiencies noted in HIV-1-infected women may be an important determinant of disease progression and survival.

Simultaneous Determination of Ascorbic Acid, Isoascorbic Acid (Erythorbic Acid) and Uric Acid in Human Plasma by High-Performance Liquid Chromatography with Amperometric Detection

Abstract A procedure is presented for the direct and simultaneous determination of ascorbic acid (AA), isoascorbic acid (IA), and uric acid (UA) in human plasma by paired-ion reversed-phase high-performance liquid chromatography. An Ultrasphere ODS (C18) column is used with a pH 5.25 mobile phase containing 0.04M sodium acetate, 0.005M tetrabutylammonium phosphate, and 0.2 mg/mL disodium EDTA. Plasma samples preserved with an equal volume of 10% metaphosphoric acid are diluted 10-fold with mobile phase and filtered through 0.2 micron filters. The injection volume is 10 uL. Detection of AA, IA, and UA is by amperometry using a glassy carbon electrode and Ag/AgCl reference electrode. The applied potential is +0.6 volt and the sensitivity setting is 100 nAmps. As little as 0.25 ng of each component can be detected at this setting and the electrode response is linear over the AA, IA, and UA ranges encountered in human plasma.

DIETARY PROTEIN‐ITS RELATIONSHIP TO VITAMIN B6 REQUIREMENTS AND FUNCTION

In the decade following the identification of vitamin Bg, it was recognized by many investigators that vitamin B6 was intimately involved Gn amino acid metabolism. Lepkovsky and Nielson first reported increased urinary excretion of xanthurenic acid from B6-deficient rats.’ Other scientists established that the addition of specific amino acids to the diet of vitamin &-deficient animals would aggravate the deficiency state. Concomitantly, it was recognized that a high protein, vitamin B6-deficient diet would hasten the onset and magnify the severity of Be deficiency in animals.2 In infants receiving a diet providing a suboptimal intake of Bg. additional dietary casein aggravated central nervous system manifestations of BG deficiency, while a high carbohydrate diet alleviated these sympt o m ~ . ~ In a study conducted at our laboratory, Harding and colleagues4 reported that human volunteers subsisting for 24 days on a packaged military ration providing 165 g of protein and 1.93 mg of vitamin B6 per day developed a statistically significant elevation of xanthurenic acid excretion after a tryptophan load at the end of the period on the diet. No significant alteration in xanthurenic acid excretion after tryptophan loading was observed in the same subjects eating a similar ration that provided 164 g of protein and 2.76 mg of vitamin B6 per day for 24 days.

Implications of nutritional status on human biochemistry, physiology, and health

Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment.

Elevated IgE level in relationship to nutritional status and immune parameters in early human immunodeficiency virus–1 disease☆☆☆★★★

Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)-1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1-seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (< 5 micrograms/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E-deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV-1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1 IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1-infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion of Thiamine and its Metabolites in the Urine of Young Adult Males Receiving Restricted Intakes of the Vitamin

Abstract : Eight young men consuming a 2800-kcal diet consisting of 80 g protein, 100 g fat and 400 g carbohydrate and providing 0.11 to 0.18 mg thiamine/day, developed clinical symptoms of thiamine deficiency in 9 to 27 days. Thiamine excreted in the urine decreased to less than 50 micrograms/day at the sixth day to the undetectable levels by the eighteenth day of depletion. Low-level repletion (0.54 to 0.61 micrograms/day) for 12 days failed to produce detectable levels of thiamine in the urine. Red blood cell transketolase activity declined with progressive thiamine deficiency and returned to normal levels with low-level repletion. The excretion of the pyrimidine and thiazole moieties of thiamine as metabolites of the vitamin appeared to increase above the levels found with the use of a diet with sufficient thiamine (about 2 mg/day), and was reduced to control levels following low-level repletion. The pyrimidine moiety in the deficient individual appears to be further catabolized. There appears to be a body store of thiamine which is utilized during a period of deficient intake. Serum cholesterol, nonesterified fatty acids, blood phospholipids, creatinine and hematocrit did not change appreciably during thiamine deficiency. The biochemical pattern for thiamine deficiency in human adults is described. (Author)