Phytonutrient deficiency: the place of palm fruit
Wattanapenpaiboon N, Wahlqvist MW
Palm fruit, one of only a few fatty fruits, is likely to have an increasingly substantiated place in human health, not only through the provision of acceptable dietary fats, but also its characteristic protective phytonutrients.

In vitro accessibility of carotenes from green leafy vegetables cooked with sunflower oil or red palm oil.
Hedrén E, Mulokozi G, Svanberg U. 2002
Although vegetables and fruits are readily available and consumed in most areas of Tanzania, vitamin A deficiency is still prevalent. The objective of the present study was to measure the in vitro accessibility (available for absorption) of alpha-carotene and beta-carotene in vegetable relishes prepared with or without oil. Derived results were used to calculate the contribution of vegetable relish to recommended daily intake of retinol. Five sundried green leafy vegetables from Tanzania were cooked without oil, with sunflower oil or with red palm oil. The total amount and in vitro accessibility of alpha-carotene and beta-carotene from a portion (100 g) of vegetable relish was determined. The in vitro method used simulated the digestion process in the gastrointestinal tract. Carotenoids released after digestion were quantified using high-performance liquid chromatography. The total amount of beta-carotene varied between 1211 and 3659 microg/100 g among the five vegetable sources studied. From green leaves cooked without oil, 8-29% of the beta-carotene content became accessible after in vitro digestion and 39-94% from leaves cooked with sunflower oil or red palm oil. Adding red palm oil instead of sunflower oil resulted in about twice as much accessible beta-carotene, due to the high accessibility of its beta-carotene content. The red palm oil contributed also a considerable amount of alpha-carotene. The results showed that by eating vegetable relishes with added oil daily, it should be possible to provide the recommended intake level of vitamin A.

Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.


Wu J1, Cho E2, Willett WC3, Sastry SM4, Schaumberg DA5.

Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.

To investigate the associations between intakes of carotenoids and AMD.

Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort.


Hayhoe RPG1, Lentjes MAH2, Mulligan AA2, Luben RN2, Khaw KT2, Welch AA1.

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), β-carotene intake (P=0·003), β-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and β-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.

Research advancements in palm oil nutrition

​Choo Yuen May and Kalanithi Nesaretnam


Palm oil is the major oil produced, with annual world production in excess of 50 million tonnes. About 85% of global palm oil produced is used in food applications. Over the past three decades, research on nutritional benefits of palm oil have demonstrated the nutritional adequacy of palm oil and its products, and have resulted in transitions in the understanding these attributes. Numerous studies have demonstrated that palm oil was similar to unsaturated oils with regards to effects on blood lipids. Palm oil provides a healthy alternative to trans-fatty acid containing hydrogenated fats that have been demonstrated to have serious deleterious effects on health. The similar effects of palm oil on blood lipids, comparable to other vegetable oils could very well be due to the structure of the major triglycerides in palm oil, which has an unsaturated fatty acid in the stereospecific numbers (sn)-2 position of the glycerol backbone. In addition, palm oil is well endowed with a bouquet of phytonutrients beneficial to health, such as tocotrienols, carotenoids, and phytosterols. This review will provide an overview of studies that have established palm oil as a balanced and nutritious oil.

Antioxidants in human health and disease.

Halliwell B1.


Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed

Tocotrienol: the natural vitamin E to defend the nervous system?
Vitamin E is essential for normal neurological function. It is the major lipid-soluble, chain-breaking antioxidant in the body, protecting the integrity of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms of primary vitamin E deficiency, it has been demonstrated that vitamin E has a central role in maintaining neurological structure and function. Orally supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a generic term for all tocopherols and their derivatives having the biological activity of RRR-alpha-tocopherol, the naturally occurring stereoisomer compounds with vitamin E activity. In nature, eight substances have been found to have vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. Often, the term vitamin E is synonymously used with alpha-tocopherol. Tocotrienols, formerly known as zeta, , or eta-tocopherols, are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Although tocopherols are predominantly found in corn, soybean, and olive oils, tocotrienols are particularly rich in palm, rice bran, and barley oils. Tocotrienols possess powerful antioxidant, anticancer, and cholesterol-lowering properties. Recently, we have observed that alpha-tocotrienol is multi-fold more potent than alpha-tocopherol in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins. At nanomolar concentration, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. Our current work identifies two major targets of tocotrienol in the neuron: c-Src kinase and 12-lipoxygenase. Dietary supplementation studies have established that tocotrienol, fed orally, does reach the brain. The current findings point towards tocotrienol as a potent neuroprotective form of natural vitamin E.

Association between leukocyte telomere length and serum carotenoid in US adults.


Min KB1, Min JY2.

Telomere length is a biomarker for aging. It is known that oxidative stress can accelerate telomere shortening, whereas antioxidants can delay their shortening. Carotenoids as antioxidants are favorably associated with health- and aging-related diseases caused by oxidative stress, but their association with telomere length is less certain. We investigated the association between blood carotenoid levels and leukocyte telomere length in a representative sample of US adults.

Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter.


Gopalan Y1, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH.

Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.

A total of 121 volunteers aged ≥35 years with cardiovascular risk factors and MRI-confirmed WMLs were randomized to receive 200 mg mixed tocotrienols or placebo twice a day for 2 years. The WML volumes were measured from MRI images taken at baseline, 1 year, and 2 years using a validated software and were compared. Fasting blood samples were collected for full blood chemistry investigation.

According to per-protocol (88 volunteers) and intention-to-treat (121 volunteers) analyses, the mean WML volume of the placebo group increased after 2 years, whereas that of the tocotrienol-supplemented group remained essentially unchanged. The mean WML volume change between the 2 groups was not significantly different (P=0.150) at the end of 1 year but was significant at the end of 2 years for both per-protocol and intention-to-treat analyses (P=0.019 and P=0.018). No significant difference was observed in the blood chemistry parameters between the 2 groups.

Mixed tocotrienols were found to attenuate the progression of WMLs.
CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00753532.

Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure.


Lee J1, Jiang S, Levine N, Watson RR.

Excessive exposure to solar radiation, especially ultraviolet A (UVA: 320-400 nm) and ultraviolet B (UVB: 290-320 nm) radiation, may induce UV-carcinogenesis and erythema in the skin. Although the protective effects of carotenoids against skin lesions are still unclear, beta-carotene has been proposed as an oral sun protectant. The purpose of this study was to determine the magnitude of the protective effects of oral alpha- and beta-carotene supplementation for 24 weeks on UVA- and UVB-induced erythema in humans. While being exposed to UVA and UVB radiation, 22 subjects (11 men and 11 women) were supplemented with natural carotenoids for 24 weeks. Each day for the first 8 weeks, subjects were given 30 mg of natural carotenoids containing 29.4 mg of beta-carotene, 0.36 mg of alpha-carotene, and traces of other carotenoids in vegetable oil. The natural carotenoid dose was progressively raised by 30-mg increments, at every 8 weeks, from 30 mg to 90 mg. Small areas (1 cm2) of the skin were exposed to increasing doses of UV light (16-42 mJ/cm2) to determine the minimal erythema dose (MED). MED was defined as a uniform pink color with well-defined borders. MED readings were obtained by visual inspection 24 hr postirradiation. Blood samples taken during supplementation were used to determine alpha- and beta-carotene serum levels and for a lipid peroxidation analysis. During natural carotenoid supplementation, the MED of solar simulator radiation increased significantly (P<0.05). After 24 weeks of supplementation, serum beta-carotene levels were increased from 0.22 microg/ml (95% CI; 0.16-0.27) to 1.72 microg/ml (95% CI;1.61-1.83). Similarly, alpha-carotene serum levels increased from 0.07 microg/ml (95% CI;0.048-0.092) to 0.36 microg/ml (95% CI; 0.32-0.40). Serum lipid peroxidation was significantly (P<0.05) inhibited in a dose-dependent manner during natural carotenoid supplementation. The present data suggest that supplementation with natural carotenoids may partially protect human skin from UVA- and UVB-induced erythema, although the magnitude of the protective effect is modest.

Serum α-carotene concentrations and risk of death among US Adults: the Third National Health and Nutrition Examination Survey Follow-up Study.


Li C1, Ford ES, Zhao G, Balluz LS, Giles WH, Liu S.


Much research has been conducted relating total carotenoids--and β-carotene in particular--to risk of cancer and cardiovascular disease (CVD). Limited data are emerging to implicate the important role of α-carotene in the development of CVD or cancer.

We assessed the direct relationship between α-carotene concentrations and risk of death among 15,318 US adults 20 years and older who participated in the Third National Health and Nutrition Examination Survey Follow-up Study. We used Cox proportional hazard regression analyses to estimate the relative risk for death from all causes and selected causes associated with serum α-carotene concentrations.

Compared with participants with serum α-carotene concentrations of 0 to 1 μg/dL (to convert to micromoles per liter, multiply by 0.01863), those with higher serum levels had a lower risk of death from all causes (P < .001 for linear trend): the relative risk for death was 0.77 (95% confidence interval, 0.68-0.87) among those with α-carotene concentrations of 2 to 3 μg/dL, 0.73 (0.65-0.83) among those with concentrations of 4 to 5 μg/dL, 0.66 (0.55-0.79) among those with concentrations of 6 to 8 μg/dL, and 0.61 (0.51-0.73) among those with concentrations of 9 μg/dL or higher after adjustment for potential confounding variables. We also found significant associations between serum α-carotene concentrations and risk of death from CVD (P = .007), cancer (P = .02), and all other causes (P < .001). The association between serum α-carotene concentrations and risk of death from all causes was significant in most subgroups stratified by demographic characteristics, lifestyle habits, and health risk factors.

Serum α-carotene concentrations were inversely associated with risk of death from all causes, CVD, cancer, and all other causes. These findings support increasing fruit and vegetable consumption as a means of preventing premature death.

Molecular mechanism of antioxidant synergism of tocotrienols and carotenoids in palm oil.

Schroeder MT, Becker EM, Skibsted LH.
May 2006
During repeated deep-fat frying of potato slices at 163 degrees C in yellow or red palm olein of comparable fatty acid profiles, the oxidative stability (peroxide value and anisidine value) of the palm oleins was similar, and in yellow palm olein, the rate of antioxidant depletion decreased in the order gamma-T3 > alpha-T3 > delta-T3 (T3, tocotrienol). In red palm olein, which had a total tocopherol/tocotrienol content of 1260 vs 940 ppm in yellow palm olein and a corresponding longer induction period in the Rancimat stability test at 120 degrees C, only depletion of gamma-T3 was significant among the phenols during frying and slower as compared to that in yellow palm olein. The carotenes in the red palm olein were depleted linearly with the number of fryings, apparently yielding an overall protection of the phenols. In antioxidant-depleted palm olein and in phospholipid liposomes with added increasing concentrations of phenols, gamma-T3 was found to be a better antioxidant than alpha-T3. alpha-T3 and alpha-T (T, tocopherol) had a similar antioxidant effect in antioxidant-depleted palm olein in the Rancimat stability test, while in the liposomes the ordering as determined by induction period for the formation of conjugated dienes was gamma-T3 > alpha-T3 > alpha-T. The addition of 100-1000 ppm beta-carotene to antioxidant-depleted palm olein or liposomes (lycopene also tested) did not provide any protection against oxidation. In the liposomes, synergistic interactions were observed between beta-carotene or lycopene and alpha-T, alpha-T3, or gamma-T3 for carotene/phenol ratios of 1:10 and 1:2 but not for 1:1. In chloroform, carotenes were regenerated by tocopherols/tocotrienols from carotene radicals generated by laser flash photolysis as shown by transient absorption spectroscopy, suggesting that carotenes rather than phenols are the primary substrate for lipid-derived radicals in red palm olein, in effect depleting carotenes prior to phenols during frying. Regeneration of carotenes by the phenols also explains the synergism in liposomes. In the laser flash photolysis experiments, gamma-T3 was also found to be faster in regenerating carotenes than alpha-T3 and alpha-T.

Dietary intake of carotenoids and risk of type 2 diabetes.


Sluijs I1, Cadier E2, Beulens JW2, van der A DL3, Spijkerman AM3, van der Schouw YT2.

Carotenoids may reduce diabetes risk, due to their antioxidant properties. However, the association between dietary carotenoids intake and type 2 diabetes risk is still unclear. Therefore, the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk.

Data from 37,846 participants of the European Prospective Investigation into Cancer and Nutrition- Netherlands study were analyzed. Dietary intakes of β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein & zeaxanthin and the sum of these carotenoids were assessed using a validated food frequency questionnaire. Incident type 2 diabetes was mainly self-reported, and verified against general practitioner information. Mean ±SD total carotenoid intake was 10 ± 4 mg/day. During a mean ±SD follow-up of 10 ± 2 years, 915 incident cases of type 2 diabetes were ascertained. After adjustment for age, sex, diabetes risk factors, dietary intake, waist circumference and BMI, higher β-carotene intakes associated inversely with diabetes risk [Hazard Ratio quartile 4 versus quartile 1 (HR(Q4)): 0.78 (95%CI:0.64,0.95), P-linear trend 0.01]. For α-carotene, a borderline significant reduced risk was observed, with a HR(Q4) of 0.85 (95%CI:0.70,1.03), and P-linear trend 0.05. β-cryptoxanthin, lycopene, lutein & zeaxanthin, and the sum of all carotenoids did not associate with diabetes risk.

This study shows that diets high in β-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women.

The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility.


van den Broek TJ#1, Kremer BHA#1, Marcondes Rezende M1, Hoevenaars FPM1, Weber P2, Hoeller U2, van Ommen B1, Wopereis S1.


Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i.e., vitamin A or retinol, vitamin D3, two homologues of vitamin E) and four carotenoids (i.e., α-carotene, β-carotene, β-cryptoxanthin, and lycopene), with characteristics of metabolic and inflammatory parameters at baseline and in response to a nutritional challenge test (NCT) in a group of 36 overweight and obese male subjects, using proteomics and metabolomics platforms. The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects.

Correlation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound. Correlation analyses of challenge response profiles for metabolite and protein parameters with micronutrient status revealed a network that is more skewed towards α-carotene and γ-tocopherol suggesting a more prominent role for these micronutrients in the maintenance of phenotypic flexibility. Comparison of the networks revealed that there is merely overlap of two parameters (inositol and oleic acid (C18:1)) affirming that there is a specific biomarker response profile upon NCT.

Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs.

Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults
Mangialasche F, Solomon A, Kåreholt I, Hooshmand B, Cecchetti R, Fratiglioni L, Soininen H, Laatikainen T, Mecocci P, Kivipelto M.
Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.

High plasma levels of vitamin E forms and reduced Alzheimer’s disease risk in advanced age
Mangialasche F, Kivipelto M, Mecocci P, Rizzuto D, Palmer K, Winblad B, Fratiglioni L
In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer’s disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated.

Palm fruit chemistry and nutrition
Sundram K, Sambanthamurthi R, Tan YA
The wide range of natural palm oil fractions, differing in their physicochemical characteristics, the most notable of which is the carotenoid-rich red palm oil further assists this. Palm vitamin E (30% tocopherols, 70% tocotrienols) has been extensively researched for its nutritional and health properties, including antioxidant activities, cholesterol lowering, anti-cancer effects and protection against atherosclerosis. These are attributed largely to its tocotrienol content.