Role of ingestible carotenoids in skin protection: A review of clinical evidence

Carotenoids, a class of phytonutrients, have been well established to boost skin's innate resistance against ultraviolet (UV) B-induced erythema (sunburn). Many of the published clinical studies thus far have focused on the measurement of erythema as the primary clinical indicator of skin protection against UVB radiation. More recent studies have shown that carotenoid supplementation provides even more skin protection than previously shown as new clinical and molecular endpoints beyond UVB-induced erythema have been reported. These recent studies have demonstrated that carotenoids also provide photoprotection against UVA-induced pigmentation and inhibit molecular markers of oxidative stress such as intercellular adhesion molecule 1, heme oxygenase-1, and matrix metalloproteinases 1 and 9. This article provides a comprehensive review of the published clinical evidence on skin benefits of carotenoids in the last five decades and indicates new perspectives on the role of ingestible carotenoids in skin protection.     

RETINOIC ACID BIOSYNTHESIS FROM RETINOL

A variety of tissues can convert retinol to retinoic acid, the highest rate being found in testis. The first enzyme in the reaction, retinol dehydrogenase, is rate limiting.     

The effect of folic acid on the development of stomach and other gast rointestinal cancers

Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal(GI)cancers.Methods In a randomized,double-blind,placebo-controlled trial,a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups:①folate(FA),20 mg per day plus vitamin B12 1 mg,intramuscularty,per month for one year,then 20 mg two times a week plus 1 mg per three months for the next year);②naural β-carotene(N-βC,30mg per day for first year,then 30mg two times a week for the next);③synthetic β-carotene(S-βC,administered as in N-βC);and ④placebo.Follow-ups continued from 1994 to 2001.Results A total of 7new cases of gastrointestinal cancers were diagnosed with 3 stomach,1 colon and 1 esophageal cancers occurring in the placebo group;1 stomach cancer in both of the N-βC and S-βC groups,and no cancer occurring if FA group.In terms of GI cancers,there was a significant reduction in the FA group,compared with the placebo group(P=0.04).A similar trend was observed in both N-βC and S-βC groups(P=0.07-0.08),Taken together,the three intervention groups displayed a highly significant decrease in occurrence(P=0.04,vs placebo),and a lower risk for GI cancers(OR=0.12;95?confidence interval,0.03-0.51).For development of gastric cancer,any one of the three active-treated groups did not reach statistically significant reduction.The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation(P=0.04).reversed intestinal metaplasia(P=0.06)at the end of follow-up,and reversed displasia(P=0.017)at 12 months.Two cases of false jaundice were found in β-carotene groups with no influence on administration,and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the development of GI cancers,a similar effect of β-carotene was also detected.Also,folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.     

Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials

Ethnopharmacological relevance

Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties.

Materials and methods

The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays.

Results

MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro.

Conclusions

Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system.     

The Role of Kola Nut (Cola Nitida) in the Etiology of Malaria Morbidity

The contribution of kola nut in mimicking malaria-like morbidity in apparently healthy volunteers was evaluated. Thirty-five grams of Cola nitida was given to each of the 48 volunteers who were known not to have taken kola nut or coffee in the previous one month for three consecutive days. The blood samples of these volunteers were enumerated for malaria parasites before serving them the kola nut. The sampling of blood was repeated on the 2nd and 3rd days for the presence of malaria parasites. Blood samples were also taken from known kola nut addicts (those that eat kola nut on daily basis). It was found that 16 (33.3%) of the volunteers had malaria parasites in their blood at the inception of the study while 32 (66.7%) had no detectable parasites. Four days after, 10 (20.8%) of the volunteers that did not show detectable parasites on the first day now had parasites. Those that showed detectable parasite before taking the kola had significant increase in parasite density. Statistical analysis showed a strong relationship between parasite increase and eating of the kola nut (Chi-squared, X 2 = 14.83, p > 0.0001 at 95% confidence limit). The volunteers reported clinical symptoms of sleeplessness, lack of concentration, dizziness, and weakness observable in malaria patients. There was no association between malaria parasite presence and clinical complaints (X 2 = 3.75, df = 1, p = 0.05). It was found that 11 people without the malaria parasite in their blood before and after taking the kola nut complained of various malaria symptoms confirming that kola nut can mimic malaria-like symptoms. In conclusion, it can be said that kola nut taken at a high concentration (about 35 g/day) will mimic malaria-like symptoms. This quantity will leave a high level of caffeine and cyanide in the circulation so that people with a low level of malaria parasite in them will notice active infection which otherwise may have been controlled by the host immune system. Lastly, the observed phenomenon can affect drug pressure and induce resistance to antimalarial drugs. The mechanism of kola nut action that influences malaria-like morbidity is discussed.     

High Serum Level of Retinol and α-Tocopherol Affords Protection Against Oral Cancer in a Multiethnic Population

Background: A comparative cross-sectional study involving oral cancer patients and healthy individuals wasdesigned to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.Materials and Methods: This study included a total of 240 matched cases and controls where subjects wereselected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopheroland β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and foodfrequency questionnaire (FFQ) respectively. Results: It was found that results from the two methods applied didnot correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels ofretinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls(0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml)were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regressionanalysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol(OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas norelationship was observed between β-carotene and oral cancer risk. Conclusions: High serum levels of retinoland α-tocopherol confer protection against oral cancer risk.     

Contribution of Dietary Intakes of Antioxidants to Homocysteine-Induced Low Density Lipoprotein (LDL) Oxidation in Atherosclerotic Patients

Purpose

Elevated circulating oxidized low density lipoprotein (Ox-LDL) levels are associated with increased risk of atherosclerosis, which may be due to high plasma homocysteine (Hcy) and low intakes of antioxidants. We investigated the contribution of dietary intakes of antioxidants to Hcy-induced LDL oxidation in atherosclerotic patients (AP) and controls.

Materials and Methods

Male AP (n = 101) who were confirmed by coronary angiography and 91 controls were evaluated by blood biochemistry and dietary intakes. To determine whether homocysteine is an independent risk factor for atherosclerosis, subjects were divided into three groups; low- (≤ 6.9 uM/L), normal- (7 uM-12 uM/L) and high- (≥ 12.1 uM/L) Hcy.

Results

Plasm levels of homocysteine and LDL were higher, but plasma apo A-I in HDL and folate were lower in the AP group. The odds ratio (OR) for the risk of atherosclerosis was 3.002 [95% confidence interval (CI), 1.27-7.09] for patients in the highest tertile with homocysteine ≥ 12.1 uM/L. AP having high homocysteine levels had low intakes of vitamin A, β-carotene and vitamin C. By logistic regression analysis, age, body mass index (BMI), plasma LDL, plasma folate, and low intakes of vitamin A and β-carotene were found to be risk factors for atherosclerosis in patients with high-Hcy, but dietary B vitamins including folate were not.

Conclusion

A high-Hcy level was a risk factor for atherosclerosis in patients with high Ox-LDL levels. High intakes of antioxidants appeared to be a protective factor for atherosclerosis, perhaps exerting a pro-oxidative effect on LDL when combined with high levels of Hcy and LDL. However, more evidence for the benefits of B vitamins as a homocysteine-lowering therapy is needed.     

Relative importance of risk factors in bladder carcinogenesis: some new results about Mediterranean habits

In the Mediterranean region of France where bladder cancer mortality and incidence are high, a case-control study with 219 male incident cases and 794 randomized, male population-controls was carried out in 1987–89 to investigate bladder cancer risk factors and more specifically, regional factors. A stepwise logistic regression was applied to the data. This investigation confirms the role of tobacco and of certain occupational exposures in bladder carcinogenesis. There was a significant dose-response relationship with lifelong coffee drinking and alcohol consumption; however the risk estimates were only significantly elevated for the heaviest drinkers. The intake of saccharin was not associated with risk of bladder cancer. Infrequent consumption of carrots, spinach, and marrows conferred an increased risk, suggesting a protective effect of vitamin A. Finally, this investigation results in some new hypotheses. The study of residences and birthplaces has revealed a lower risk for those who have lived in a non-Mediterranean area and a higher risk for those born in a Mediterranean area. These features might be explained by some Mediterranean dietary habits, such as a high consumption of spices (odds ratio =3.64, 95 percent confidence interval=2.21–5.98).This study was supported by a grant from the Institut National de la Santé et de la Recherche Médicale (INSERM).     

Dietary retinol: prevention or promotion of carcinogenesis in humans?

A number of epidemiologic studies have found that vitamin A is associated with a reduced risk for human cancers. Dietary vitamin A indices reflect intake of several compounds in the diet including retinol and provitamin A carotenoids such as -carotene, and recent cancer epidemiology studies have attempted to distinguish effects of retinol from those of -carotene. While -carotene has been associated consistently with a reduced risk for a number of human cancers, particularly epithelial cancers, retinol is generally found to be unassociated with, or positively associated with, risk for many cancers. An apparent enhancement of carcinogenesis has been observed in numerous studies, particularly of cancer of the esophagus, oral cavity, pharynx, larynx, stomach, colon, and rectum. While this finding could be artifactual, experimental studies in animals as well as mechanistic considerations suggest that this effect deserves serious consideration. As discussed in this article, an apparent enhancement of carcinogenesis could be related to an ethanol/retinol interaction, and/or a mechanism involving pro-oxidant activity of retinol but anti-oxidant activity of -carotene. This article concludes with suggestions for further research to help clarify the association between retinol and human carcinogenesis.Des Mayne and Zheng are in the Department of Epidemiology and Public Healtb, Yale University School of Medicine. Dr Grabam is in the Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA. Address correspondence to Dr Mayne at the Department of Epidemiology and Public Health, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510, USA. The research was supported by NIH grant CA-42101.     

Bioefficacy of β-carotene is improved in rats after solubilized as equimolar dose of β-carotene and lutein in phospholipid-mixed micelles

β-Carotene (BC) is a potent dietary source of vitamin A for populations at risk of vitamin A deficiency, yet its bioavailability is influenced by several factors such as dietary fat, carotenoids type, and other components. We hypothesize that type of micellar phospholipids influence bioefficacy of carotenoids and activity of carotenoid metabolizing enzymes. This study determined the BC bioefficacy in rats (n = 5/time point) after an equimolar dose of BC and lutein (Lut) solubilized in micelles containing either phosphatidylcholine (PC) or lysophosphatidylcholine (LPC), or no phospholipid (NoPL). Results show that no BC and Lut was detected in the plasma of rats at 0 hour, but after gavage, the mean (SD) area under the curve (AUC; in picomoles per milliliter) of plasma BC for 6 hours in PC, LPC, and NoPL groups were 1145 (132), 965 (199), and 2136 (112), respectively. The AUC value of plasma Lut in LPC group (183 ± 23 pmol mL⁻¹ h⁻¹) was higher than the other 2 groups. Similarly, liver BC and Lut levels in the LPC group were significantly higher than the other groups. The activity of BC 15,15′-monooxygenase in the intestinal mucosa of LPC and PC groups was higher than NoPL group. Plasma retinyl palmitate level in LPC (AUC, 647 ± 89 pmol mL⁻¹ h⁻¹) group was 2-fold higher than that of PC and NoPL groups. Results indicate that phospholipids enhanced the BC and Lut absorption. β-Carotene uptake was not affected by Lut when given with micellar phospholipids, but reduced plasma Lut level was observed, which may be due to the conversion of absorbed Lut into its metabolites.