Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study.

The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate-specific antigen (PSA) levels. We have studied the effect of a dietary supplement (verum, administered for 6 weeks) containing plant estrogens, antioxidants, including carotenoids, selenium and other putative prostate cancer inhibiting substances in a randomized placebo-controlled double-blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels. Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels. Male sex hormone levels were significantly lower during the verum phase (DHT: -0.11 nmol/L, p = 0.005; testosterone: -1 nmol/L, p = 0.02). Total PSA doubling time was unaffected. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half-life of 13 weeks; p = 0.02). In those men in whom the free androgen index decreased (21 out of 32), a significant decrease in the slopes of both total and free PSA was observed (p = 0.04). Overall total PSA doubling times did not increase significantly during verum. However, the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time (and total PSA doubling time in a relevant subgroup). If future studies confirm that these observations translate into a slowing of disease progression, a dietary intervention may become an attractive option for prostate cancer treatment and prevention.

Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation.

BACKGROUND: Endothelial cell dysfunction may be related to an increase in cellular oxidative stress. Carotenoids and vitamins could have an antioxidant-mediated tempering influence on endothelial function and inflammation, thereby reducing the risk of atherosclerosis. METHODS: We measured serum carotenoids, alpha-tocopherol and Vitamin C concentrations in 379 subjects sampled from the general population. High-sensitive C-reactive protein (CRP), fibrinogen (Fbg) and leukocytes were measured as markers of inflammation. Furthermore, soluble intercellular adhesion molecule-1 (sICAM-1) and flow-mediated vasodilation (FMD; n= 165) were measured as markers of endothelial function. Relationships between serum carotenoids and vitamins and markers of endothelial function and inflammation were analysed after adjustment for confounding. RESULTS: In the total study group, lutein and lycopene were inversely related to sICAM-1 with regression-coefficients of -0.38+/-0.19 (p = 0.04) and -0.16+/-0.08 (p = 0.04) per 1 micromol/l, respectively. beta-Carotene was inverse related to leukocytes (-0.23+/-0.07; p = 0.007) and CRP (-1.09+/-0.30; p = 0.0003) per 1 micromol/l. Vitamin C was inverse related to CRP (-0.01+/-0.005; p = 0.04) per 1 micromol/l, whereas alpha-tocopherol was positively related to CRP (0.03+/-0.01; p = 0.02) per 1 micro/l. Zeaxanthin was inversely related to FMD (31.2+/-15.3; p = 0.04) per 1 micromol/l. CONCLUSION: The inverse relations between carotenoids, Vitamin C and sICAM-1, CRP and leukocytes may help to explain the possible protective effect of carotenoids and Vitamin C on atherosclerosis through an influence on inflammatory processes and endothelial function.

Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults.

BACKGROUND: High doses of vitamin E have been shown to decrease lipid peroxidation in persons under oxidative stress. At present, the data are insufficient to predict whether lower doses offer the same benefit in healthy persons. OBJECTIVE: We studied the effect of moderate doses of a combination of vitamin E and carotenoids, incorporated into a food product, on markers of antioxidant status and lipid peroxidation in healthy persons. DESIGN: One hundred five healthy adults were randomly, evenly assigned in this double-blind, placebo-controlled, parallel, 11-wk intervention study. After a 2-wk stabilization period during which the subjects consumed a commercial unfortified spread, the subjects consumed 25 g/d of spread containing 43 mg alpha-tocopherol equivalents (alpha-TE; 2-3 fold the US dietary reference intake) and 0.45 mg carotenoids (spread A), 111 mg alpha-TE and 1.24 mg carotenoids (spread B), or 1.3 mg RRR-alpha-tocopherol without carotenoids (spread C). RESULTS: In subjects consuming spread A, plasma alpha-tocopherol concentrations increased 31% to 32 micromol/L, with small but significant increases in concentrations of alpha-carotene and lutein. This resulted in LDL with significantly higher total antioxidant capacity (17%) and an increased resistance to oxidation, as determined by lag time (18%). These improvements were dose dependent: larger increases in these variables were observed in subjects consuming spread B. Furthermore, consumption of spread B significantly reduced concentrations of the plasma lipid peroxidation biomarker F(2 alpha)-isoprostane (15%). CONCLUSION: The consumption of food products containing moderate amounts of vitamin E and carotenoids can lead to measurable and significant improvements in antioxidant status and biomarkers of oxidative stress in healthy persons.

Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans.

Excessive consumption of energy and fat increases the risk for obesity. Snacks containing sucrose polyesters (SPE) as a dietary fat replacer are on the market in the United States. SPE products have been shown to lower concentrations of serum carotenoids in short-term studies. Experimental studies on the longer-term effects on health of decreased carotenoid concentrations are lacking. A 1-y randomized, double-blind, placebo-controlled parallel trial was performed. Subjects (n = 380) with a habitual low or high fruit and vegetable intake were assigned to the treatments (0, 7, 10 or 17 g/d SPE). SPE was given in the form of spreads, chips or both. The groups were compared for serum carotenoids, vitamins and markers of oxidative damage, eye health, cardiovascular health and immune status. After 1 y, serum lipid-adjusted carotenoids showed the largest decrease in the SPE chips and spread group (17 g/d) compared with the control group [alpha-carotene 33%; beta-carotene 31%, lycopene 24%, beta-cryptoxanthin 18%, lutein 18% (all P < 0.001) and zeaxanthin 13% (P < 0.05)]. Consumption of SPE spread (10 g/d SPE) decreased carotenoid concentrations by 11-29% (all P < 0.05). SPE chips (7 g/d SPE) decreased zeaxanthin (11%), beta-carotene (12%) and alpha-carotene (21%; all P < 0.05). Serum lipid adjusted alpha-tocopherol decreased significantly by 6-8% (all P < 0.001) in all SPE groups. No negative effects were observed on markers of oxidation, eye health, cardiovascular health or immune status. This study shows that decreases in serum carotenoid concentrations do not affect possible markers of disease risk.

Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin.

BACKGROUND: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxanthin and adipose lutein concentrations in a general population. OBJECTIVE: The objective was to investigate the associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein, taking into account potential confounders in a population. DESIGN: Volunteers (n = 376) aged 18-75 y were recruited. In a cross-sectional design, serum (n = 376) and adipose tissue (n = 187) were analyzed for carotenoids, and MP density was measured by spectral fundus reflectance. RESULTS: Mean MP density in the total study group was 0.33 +/- 0.15. MP density was 13% higher in men than in women (P < 0.05). Serum and blood concentrations of alpha-tocopherol, vitamin C, and all carotenoids except lycopene were significantly higher in women. Adipose lutein concentrations were also significantly higher in women than in men. Regression models showed a positive significant association between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations in men after adjustment for age, but no relation in women. In men, serum lutein remained significantly associated with MP density after adjustment for age, total cholesterol, body mass index, and smoking. CONCLUSION: The associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations are stronger in men than in women.

Olive oil phenolics protect LDL and spare vitamin E in the hamster.

An animal feeding trial was conducted to investigate whether olive oil phenolics can act as functional antioxidants in vivo. To this end, hamsters were exposed for a period of 5 wk to a dietary regime with either a phenol-rich extra virgin olive oil or extra virgin olive oil from which phenols were removed by ethanol/water-washing. The original oil used in the high olive phenol diet was also used for the preparation of the low phenol diet in order to keep the FA compositions exactly the same. In addition, the vitamin E content was kept identical in both diets. This careful preparation of the diets was undertaken in order to prevent these factors from influencing the antioxidative status in plasma and LDL. Removal of olive oil phenols was shown to reduce both the vitamin E level in plasma and the resistance of LDL to ex vivo oxidation. The results of this study support the idea that extra virgin olive oil phenols improve the antioxidant defense system in plasma by sparing the consumption of vitamin E under normal physiological circumstances.