HOME            DETAILED RESEARCH




















































































































(TEXT BASED)

TOUR TABS B12 ULTRA FRUIT LOZENGES

NUTRITION ANALYSIS

AND SUPPORTING RESEARCH

 

 

            Tour Tabs B12 Ultra Fruit Energizer Lozenges  …the perfect tool for maintaining and improving performance of field personnel through advanced scientific nutrition. 

            The immune system of the human body is the most critical piece if the human puzzle; unless it is functioning optimally, the human body can suffer a vast array of breakdowns due to exhaustion, disease, mental acuity, and physical function.  In perfect working order, the immune system fights off fatigue, bacterial and viral infection, maintains internal chemical balances and improves body function overall.  An enormously complex mechanism, the immune systems consist of many types of proteins, cells, organs, and tissues which interact in an elaborate and dynamic network to “keep the body healthy”.

            Using the science of advanced nutrition, Tour Tabs B12 Ultra Fruit Energizer Lozenges bring to bear over a dozen vitamins and fruit extracts that boost the immune system, energize the body and mind and help to improve the overall efficiency of field personnel by keeping their brains sharp and their bodies in maximum healthy condition. 

            In the field, any form of illness, even the common cold, directly affects decision-making, response time and hand-eye coordination.  Exhaustion has a similar effect, causing personnel to operate below optimal efficiency, possibly putting themselves and others at risk. 

            Tour Tabs, a delicious and satisfying lozenge dissolved by mouth, contains 4 B-Vitamins as well as a concentrated fruit extracts. There is much long-term clinical nutritional analysis demonstrating that the B Vitamins in Tour Tabs enhance immune and nervous system function, and combat the symptoms and causes of stress, depression and cardiovascular disease. In addition, Tour Tabs contains over 5,000 milligrams per serving of concentrated fruit extracts that have been shown in clinical research to have significant anti-oxidant/immune-boosting effects, anti-cancer properties, disease-prevention, cholesterol-reduction and increased physical endurance.  Because mental acuity, endurance and overall health and wellbeing are critical to the performance of field personnel, Tour Tabs have been created to promote those optimal health conditions for a more effective military.

 

 

Primary ingredients: Goji Berry, Pomegranate, Mangosteen, Acai Berry, Noni, Camu Camu, Cranberry, Resveratrol, B12, B6, Folic Acid, Biotin

 

 

GOJI BERRY:

 

SUMMARY:

 

Goji Berry (also called Lycium barbarum) polysaccharides show significant antioxidant activity2,3, as well as increases in energy level, athletic performance, mental acuity and reduction in fatuigue1.  Goji fruits also contain zeaxanthin, an important dietary carotenoid selectively absorbed into the retinal macula lutea where it is thought to provide antioxidant and protective light-filtering roles. A human supplementation trial showed that daily intake of goji increased plasma levels of zeaxanthin.  Several published studies have also reported possible medicinal benefits of Goji, especially due to its antioxidant properties, including potential benefits against cardiovascular and inflammatory diseases, vision-related diseases, having neuroprotective properties or as an anticancer and immunomodulatory agent2.

 

 

POMEGRANATE:

 

SUMMARY:

 

Pomegranate aril is high in vitamin C and is a good source of vitamin B5 (pantothenic acid), potassium and antioxidant polyphenols4. The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called punicalagins which have free-radical scavenging properties. Punicalagins are absorbed into the human body and may have dietary value as antioxidants.  In preliminary laboratory research and human pilot studies, pomegranate has been found effective in reducing heart disease risk factors, including LDL oxidation, macrophage oxidative status, and foam cell formation, all of which are steps in atherosclerosis and cardiovascular disease5,6. In addition Pomegranate has been shown to be an effective anti-cancer agent7.

 

 

MANGOSTEEN:

 

SUMMARY:

 

Mangosteen contains xanthones and there are significant indications that the potential benefit of xanthones as antioxidant phytochemicals are uuseful to human health and appear promising.  Xanthone extracts taken from the Mangosteen pericarp and added to a juice show indications of  beneficial anti-oxidant activity8,10.   Initial medical research on mangosteen and its xanthones is a relatively young scientific field with promising evidence for anti-disease properties established to date. In recent years, mangosteen has attracted special attention for its xanthone extracts - garcinol and mangostin - having potential as anti-inflammatory agents with preliminary evidence for inhibiting cyclo-oxygenase (COX) enzymes and carcinogens9.

 

 

 

 

ACAI BERRY:

 

SUMMARY:

 

Acaí fruit has dense contents of polyphenols such as procyanidin oligmers and vanillic acid, syringic acid, p-hydroxybenzoic acid, protocatechuic acid. Açaí has a strong intermediate antioxidant potency among juices, and a powdered preparation of freeze-dried açaí fruit pulp and skin was shown to contain anthocyanins (3.19 mg/g), including cyandin 3-glucoside and cyanidin 3-rutinoside11,12. In a study of açaí for their antioxidant capacity, it was found to have proved excellent against peroxyl radicals, as well as good against peroxynitrite13. Freeze-dried açaí powder was found to have high antioxidant activity against superoxide (1614 units/g) and peroxyl radicals (1027 μmol TE/g) and milder activity for peroxynitrite and hydroxyl radicals.  Studies have demonstrated that blood antioxidant capacity increases within two hours of consuming açaí. Freeze-dried açaí powder was shown to have mild inhibitory effects on cyclooxygenase enzymes COX-1 and COX-2, and chemically-extracted polyphenolic-rich fractions from açaí were reported to reduce the proliferation of HL-60 (experimental leukemia) cells in vitro

 

 

 

NONI FRUIT:

 

SUMMARY:

 

Noni has increasingly stimulated the interest of medical science, with 145 papers published since 1994 and 55 just since 2006.  A university-based pilot study has shown that noni juice consumption may lower blood cholesterol levels.Laboratory studies have investigated noni's effect on the growth of cancerous tissue in mice16.  The same study showed effective antioxidant properties of noni juice compared with those of vitamin C, grape seed powder, and pycnogenol. The results indicated reduced carcinogen-DNA adduct formation in this laboratory model and antioxidant activity that may be relevant to anti-cancer mechanisms15. Laboratory experiments showed that noni juice may affect physical endurance of mice and a preliminary study of athletes showed potential benefit of noni juice on exercise endurance, an effect the authors attributed to increased antioxidant capacity14.

 

 

CAMU CAMU:

 

 

SUMMARY:

 

Camu Camu contains an extraordinarily high Vitamin C content (in the order of 2-3% of fresh weight) and is the most important property of the camu camu fruit. As a myrtaceous fruit, camu camu also provides other nutritional benefits (phenolics, etc.,). but the natural Vitamin C is the key element to its high anti-oxidant properties17,18.  In addition to the high vitamin C content it contains the amino acids valine, leucine and serine, and is also rich in flavonoids.

 

Vitamin C has been researched for years and been well established as one of the premier anti-oxidants.  Vitamin C or L-ascorbate is an essential nutrient for a large number of higher primate species, a small number of other mammalian species (notably guinea pigs and bats), a few species of birds, and some fish. The presence of ascorbate is required for a range of essential metabolic reactions in all animals and plants.

 

 

 

CRANBERRY:

 

SUMMARY:

 

Cranberries are a source of polyphenol antioxidants, phytochemicals under active research for possible benefits to the cardiovascular system, immune system and as anti-cancer agents19. Cranberry juice contains a chemical component, a high molecular weight non-dializable material (NDM), as noted above, that is able to inhibit and even reverse the formation of plaque by Streptococcus mutan pathogens that cause tooth decay. Cranberry juice components also show efficacy against formation of kidney stones.

 

Cranberries are abundant food sources of the anthocyanidin flavonoids, cyanidin, peonidin and quercetin. These compounds have been proven powerful against human cancer cells in vitro. There has been an increasing focus on the potential role of cranberry polyphenolic constituents in preventing several types of cancer.

 

There is potential benefit of cranberry juice consumption against bacterial infections in the urinary system. While much of the evidence is equivocal, hypotheses state that an effect occurs from a component of the juice competitively inhibiting bacterial attachment to the bladder and urethra, allowing the bacteria to be flushed out more easily.

 

In April 2004, the French government agency AFSSA, which regulates food products in a way similar to the United States FDA, granted approval of cranberry juice as an antibacterial agent for urinary tract health20.

 

To date, four completed randomized clinical trials have shown evidence for inhibiting bacterial infections in the urinary tract of women by drinking cranberry juice over a 12 month period.

 

RESVERATROL:

 

 

SUMMARY:

 

Resveratrol is a natural antioxidant found in red wine and red grape skins, with studies suggesting it protects against a range of illnesses and diseases including neurodegenerative diseases such as Parkinson's or other dementias, cancer and heart disease and more recently documented for its role in extending lifespan22. Resveratrol is a molecule so tiny that it penetrates the wall of almost any cell in an organism where it continues into the cell nucleus. There, resveratrol selectively switches on genes that aid the survival of an organism, like the Sirtuin 1 DNA-repair gene21. Using gene silencing, it switches off genes involved in the initiation and progression of disease, blocking replication of bacteria, viruses, fungi and tumor cells23. New studies in small animals show it slows the onset of virtually all of the aging diseases: heart, arthritis, cancers, and Alzheimer's.   In addition, recent studies indicate that Resveratrol increases endurance as well.

 

B12, B6,  FOLIC ACID, BIOTIN24-28:

 

The B vitamins often work together to deliver a number of health benefits to the body. B vitamins have been shown to support and increase the rate of metabolism, maintain healthy skin and muscle tone,

enhance immune and nervous system function, promote cell growth and division — including that of the red blood cells that help prevent anemia, reduce the risk of pancreatic cancer, one of the most lethal forms of cancer.  Together, they also help combat the symptoms and causes of stress, depression, and cardiovascular disease.

 

All B vitamins are water soluble, and are dispersed throughout the body. Most of the B vitamins must be replenished daily, since any excess is excreted in the urine.  Vitamin B-12 is normally involved in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production. Many (though not all) of the effects of functions of B-12 can be replaced by sufficient quantities of folic acid (another B vitamin), since B-12 is used to regenerate folate in the body.

 

 

 

RESEARCH NOTATIONS:

 

1: J Altern Complement Med. 2008 May;14(4):403-12.

 

A randomized, double-blind, placebo-controlled, clinical study of the general effects of a standardized Lycium barbarum (Goji) Juice, GoChi.

 

Amagase H, Nance DM.

FreeLife International, LLC, Phoenix, AZ 85040, USA. hamagase@freelife.com

 

BACKGROUND: This randomized, double-blind, placebo-controlled clinical trial is the first study reported from outside China that has examined the general effects of the orally consumed goji berry, Lycium barbarum, as a standardized juice (GoChi; FreeLife International LLC, Phoenix, AZ) to healthy adults for 14 days. METHODS: Based upon the medicinal properties of Lycium barbarum in traditional Asian medicine, we examined by questionnaire subjective ratings (0-5) of general feelings of well-being, neurologic/psychologic traits, gastrointestinal, musculoskeletal, and cardiovascular complaints as well as any adverse effects. Also, measures of body weight, body-mass index, blood pressure, pulse rate, and visual acuity were assessed before and after consuming 120 mL of GoChi/day or placebo control solution. Data were statistically analyzed for changes between day 1 and day 15. RESULTS: Significant differences between day 1 and day 15 were found in the GoChi group (N = 16) in increased ratings for energy level, athletic performance, quality of sleep, ease of awakening, ability to focus on activities, mental acuity, calmness, and feelings of health, contentment, and happiness. GoChi also significantly reduced fatigue and stress, and improved regularity of gastrointestinal function. In contrast, the placebo group (N = 18) showed only two significant changes (heartburn and happiness). No significant changes in musculoskeletal or cardiovascular complaints were observed in either group. All parametric data (body weight, etc.) were not significantly different between groups or between day 1 and day 15 for either group. CONCLUSIONS: These results clearly indicate that daily consumption of GoChi for 14 days increases subjective feelings of general well-being, and improves neurologic/psychologic performance and gastrointestinal functions. The data strongly suggest that further research is indicated to confirm and extend knowledge of the potential effects of Lycium barbarum upon human health.

 

2: Int Immunopharmacol. 2004 Apr;4(4):563-9.

 

Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum.

 

Gan L, Hua Zhang S, Liang Yang X, Bi Xu H.

Institute of Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China. ganlu07@163.com

 

The modulation of a polysaccharide-protein complex from Lycium barbarum (LBP3p) on the immune system in S180-bearing mice was investigated. The mice inoculated with S180 cell suspension were treated p.o. with LBP3p (5, 10 and 20 mg/kg) for 10 days. The effects of LBP3p on transplantable tumors and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells (QHS), lymphocyte proliferation, the activity of cytotoxic T lymphocyte (CTL), interleukin-2 (IL-2) gene expression and lipid peroxidation were studied. LBP3p could significantly inhibit the growth of transplantable sarcoma S180 and increase macrophage phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte proliferation, CTL activity, IL-2 mRNA expression level and reduce the lipid peroxidation in S180-bearing mice. The effect is not dose-dependent in a linear fashion. A total of 10 mg/kg dose is more effective than 5 and 20 mg/kg doses. This suggests that LBP3p at 10 mg/kg has a highly significant effect on tumor weight and improves the immune system. Copyright 2004 Elsevier B.V.

 

3: Phytother Res. 2004 Dec;18(12):1008-12. (excerpts specific to LB)

 

Antioxidant activities of some common ingredients of traditional chinese medicine, Lycium barbarum (LB).

 

Wu SJ, Ng LT, Lin CC.

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.

 

The antioxidant activities of Lycium barbarum (LB) and two other ingredients were evaluated in this study. The results showed that aqueous extracts of these crude drugs exhibited antioxidant activities in a concentration-dependent manner. All extracts displayed an inhibitory effect on FeCl2-ascorbic acid induced lipid peroxidation in rat liver homogenate in vitro, with the order of activity LB > AS > PC. The tested extracts showed a superoxide anion scavenging activity ranging from 28.8% to 82.2% and anti-superoxide activity varying from 38.0% to 84.5%. Among the different extracts, LB extract exhibited the lowest IC50 values (0.77-2.55 microg/mL) in all model systems tested in this study. The present study concludes that LB extract possessed the strongest inhibition on malondialdehyde formation in rat liver homogenate, and superoxide anion scavenging and anti-superoxide formation activities. These results also suggest that LB extract is a good source of antioxidant agent in the daily dietary supplement. 2004 John Wiley & Sons, Ltd.

 

4: J Agric Food Chem. 2006 Nov 15;54(23):8956-61.

 

Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers.

 

Mertens-Talcott SU, Jilma-Stohlawetz P, Rios J, Hingorani L, Derendorf H.

Pharmaceutics Department, University of Florida, Gainesville, Florida 32610, USA. smertens@ufl.edu

 

The intake of polyphenols has been demonstrated to have health-promoting and disease-preventive effects. The pomegranate (Punica granatum L.), which is rich in several polyphenols, has been used for centuries in ancient cultures for its medicinal purposes. The potential health benefits of pomegranate polyphenols have been demonstrated in numerous in vitro studies and in vivo experiments. This study investigated the absorption and antioxidant effects of a standardized extract from pomegranate in healthy human volunteers after the acute consumption of 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h. The plasma metabolites urolithin A, urolithin B, hydroxyl-urolithin A, urolithin A-glucuronide, and dimethyl ellagic acid-glucuronide were identified by HPLC-MS. The antioxidant capacity measured with the oxygen radical absorbance capacity (ORAC) assay was increased with a maximum effect of 32% after 0.5 h, whereas the generation of reactive oxygen species (ROS) was not affected. The inflammation marker interleukin-6 (IL-6) was not significantly affected after 4 h after the consumption of the extract. Overall, this study demonstrated the absorbability of EA from a pomegranate extract high in ellagitannin content and its ex vivo antioxidant effects.

 

5: Clin Nutr. 2004 Jun;23(3):423-33.

 

Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation.

 

Aviram M, Rosenblat M, Gaitini D, Nitecki S, Hoffman A, Dornfeld L, Volkova N, Presser D, Attias J, Liker H, Hayek T.

The Lipid Research Laboratory, Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel. aviram@tx.technion.ac.il

 

Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with PJ for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during PJ consumption. In the control group that did not consume PJ, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The patients' serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas serum LDL basal oxidative state and LDL susceptibility to copper ion-induced oxidation were both significantly reduced, by 90% and 59%, respectively, after 12 months of PJ consumption, compared to values obtained before PJ consumption. Furthermore, serum levels of antibodies against oxidized LDL were decreased by 19%, and in parallel serum total antioxidant status (TAS) was increased by 130% after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year of PJ consumption by 21% and was not further reduced along 3 years of PJ consumption. For all studied parameters, the maximal effects were observed after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had no additional beneficial effects on IMT and serum PON1 activity, whereas serum lipid peroxidation was further reduced by up to 16% after 3 years of PJ consumption. The results of the present study thus suggest that PJ consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to the potent antioxidant characteristics of PJ polyphenols.

 

6: J Nutr. 2001 Aug;131(8):2082-9.

 

Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis.

 

Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, Aviram M.

The Lipid Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa 31096, Israel.

 

Inhibition of lipid peroxidation contributes to the attenuation of macrophage cholesterol accumulation, foam-cell formation and atherosclerosis. Evidence suggests that nutritional antioxidants such as pomegranate juice (PJ) can contribute to the reduction of oxidative stress and atherogenesis. The goals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E(0)) mice with advanced atherosclerosis and to analyze the antiatherosclerotic activity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemented with PJ in their drinking water for 2 mo and compared with age-matched placebo-treated mice, as well as to young (4-mo-old) control mice, for their mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and mice atherosclerotic lesion size. PJ supplementation reduced each of the proatherogenic variables determined in the present study compared with age-matched placebo-treated mice. It significantly induced serum paraoxonase activity and reduced MPM lipid peroxide content compared with placebo-treated mice and control mice. PJ administration to E(0) mice significantly reduced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterification and increased macrophage cholesterol efflux by 39% compared with age-matched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL uptake and cholesterol esterification to levels lower than those in 4-mo-old, unsupplemented controls. PJ supplementation to E(0) mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treated mice. In a separate study, supplementation of young (2-mo-old) E(0) mice for 2 mo with a tannin fraction isolated from PJ reduced their atherosclerotic lesion size, paralleled by reduced plasma lipid peroxidation and decreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced atherosclerosis reduced their macrophage oxidative stress, their macrophage cholesterol flux and even attenuated the development of atherosclerosis. Moreover, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity.

 

7: Public release date: 26-Sep-2005

 

Contact: Lisa Brunette

la.brunette@hosp.wisc.edu

608-263-5830

University of Wisconsin-Madison

 

MADISON - The juice of the pomegranate, say researchers at University of Wisconsin Medical School, shows major promise to combat prostate cancer - the most common invasive cancer and the second-leading cause of cancer death in American men.

With more than 230,000 new cases of prostate cancer expected to be diagnosed this year alone in the U.S. and the outlook poor for patients with metastatic disease, researchers are looking for new strategies to combat the disease. Earlier research at Wisconsin and elsewhere has shown that the pomegranate, a fruit native to the Middle East, is rich in anti-oxidant and anti-inflammatory activity and is effective against tumors in mouse skin. In fact, pomegranate juice has higher anti-oxidant activity than do red wine and green tea, both of which appear promising as anti-cancer agents.

 

The UW research team aimed to find out if the extract from pomegranates would not only kill existing cancer, but help prevent cancer from starting or progressing. Using human prostate cancer cells, the team first evaluated the fruit extract's effect, at various doses, on those cells cultured in laboratory dishes. They found a "dose-dependent" effect - in other words, the higher the dose of pomegranate extract the cells received, the more cells died.

 

The research team then progressed to tests in mice that had been injected with prostate cancer cells from humans and developed malignancies. The 24 mice were randomly divided into three groups. The control group received normal drinking water, while the animals in the second and third groups had their drinking water supplemented with .1 percent and .2 percent pomegranate extract respectively. The doses for the mice were chosen to parallel how much pomegranate juice a typical healthy human might be willing to eat or drink daily.

 

The results were dramatic: the mice receiving the higher concentration of pomegranate extract showed significant slowing of their cancer progression and a decrease in the levels of prostate-specific antigen (PSA), a marker used to indicate the presence of prostate cancer in humans. The animals that received only water had tumors that grew much faster than those in the animals treated with pomegranate extract.

 

"Our study - while early -- adds to growing evidence that pomegranates contain very powerful agents against cancer, particularly prostate cancer," says lead author Dr. Hasan Mukhtar, professor of dermatology in the UW Medical School. "There is good reason now to test this fruit in humans - both for cancer prevention and for treatment."

 

The next step in the evaluation of pomegranates for cancer prevention and treatment is to conduct tests in humans, according to Mukhtar.

 

8: Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem. 2006 Mar 22;54(6):2077-82.

 

9: Liao CH, Sang S, Liang YC, Ho CT, Lin JK. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by Garcinol. Mol Carcinog. 2004 Nov;41(3):140-9.

 

10: Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL. Lipophilic and hydrophilic antioxidant capacities of common foods in the United States.  J Agric Food Chem. 2004 Jun 16;52(12):4026-37

 

11: J Agric Food Chem. 2008 Aug 12. [Epub ahead of print]

 

Pharmacokinetics of Anthocyanins and Antioxidant Effects after the Consumption of Anthocyanin-Rich Acai Juice and Pulp (Euterpe oleracea Mart.) in Human Healthy Volunteers.

 

Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P, Pacheco-Palencia LA, Meibohm B, Talcott ST, Derendorf H.

smtalcott@tamu.edu.

 

The acai berry is the fruit of the acai palm and is traditionally consumed in Brazil but has gained popularity abroad as a food and functional ingredient, yet little information exists on its health effect in humans. This study was performed as an acute four-way crossover clinical trial with acai pulp and clarified acai juice compared to applesauce and a non-antioxidant beverage as controls. Healthy volunteers (12) were dosed at 7 mL/kg of body weight after a washout phase and overnight fast, and plasma was repeatedly sampled over 12 h and urine over 24 h after consumption. Noncompartmental pharmacokinetic analysis of total anthocyanins quantified as cyanidin-3- O-glucoside showed C max values of 2321 and 1138 ng/L at t max times of 2.2 and 2.0 h, and AUC last values of 8568 and 3314 ng h L (-1) for pulp and juice, respectively. Nonlinear mixed effect modeling identified dose volume as a significant predictor of relative oral bioavailability in a negative nonlinear relationship for acai pulp and juice. Plasma antioxidant capacity was significantly increased by the acai pulp and applesauce. Individual increases in plasma antioxidant capacity of up to 2.3- and 3-fold for acai juice and pulp, respectively were observed. The antioxidant capacity in urine, generation of reactive oxygen species, and uric acid concentrations in plasma were not significantly altered by the treatments. Results demonstrate the absorption and antioxidant effects of anthocyanins in acai in plasma in an acute human consumption trial.

 

 

12: J Agric Food Chem. 2008 May 28;56(10):3593-600. Epub 2008 Apr 29.

 

Absorption and biological activity of phytochemical-rich extracts from açai (Euterpe oleracea Mart.) pulp and oil in vitro.

 

Pacheco-Palencia LA, Talcott ST, Safe S, Mertens-Talcott S.

Department of Nutrition and Food Science and Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843, USA.

 

Polyphenolic extracts from various fruits and vegetables have been shown to exert growth inhibitory effects in cell culture studies. Whereas individual polyphenolic compounds have been extensively evaluated, understanding of the biological activity of polyphenolic extracts from natural sources is limited and critical to the understanding of their potential effects on the human body. This study investigated the absorption and antiproliferative effects of phytochemical extracts from acai pulp and a polyphenolic-enriched acai oil obtained from the fruit pulp of the acai berry ( Euterpe oleracea Mart.). Chemical composition, antioxidant properties, and polyphenolic absorption of phytochemical fractions in a Caco-2 monolayer were determined, along with their cytotoxicity in HT-29 human colon adenocarcinoma cells. Standardized extracts were characterized by their predominance of hydroxybenzoic acids, monomeric flavan-3-ols, and procyanidin dimers and trimers. Polyphenolic mixtures (0-12 microg of gallic acid equiv/mL) from both acai pulp and acai oil extracts inhibited cell proliferation by up to 90.7%, which was accompanied by an increase of up to 2.1-fold in reactive oxygen species. Absorption experiments using a Caco-2 intestinal cell monolayer demonstrated that phenolic acids such as p-hydroxybenzoic, vanillic, syringic, and ferulic acids, in the presence of DMSO, were readily transported from the apical to the basolateral side along with monomeric flavanols such as (+)-catechin and (-)-epicatechin. Results from this study provide further evidence for the bioactive properties of acai polyphenolics and offer new insight on their composition and cellular absorption.

 

13: J Agric Food Chem. 2006 Nov 1;54(22):8604-10.

 

Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai).

 

Schauss AG, Wu X, Prior RL, Ou B, Huang D, Owens J, Agarwal A, Jensen GS, Hart AN, Shanbrom E.

Natural and Medicinal Products Research, AIMBR Life Sciences, 4117 South Meridian, Puyallup, Washington 98373, USA. alex@aibmr.com

 

The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into "slow-acting" and "fast-acting" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.

 

14: Accepted 10 July 2008 - Morinda citrifolia L. (noni) improves athlete endurance: Its mechanisms of action

'Afa K. Palu1*, R. D. Seifulla2 and. Brett J. West

Tahitian Noni International Research Center, American Fork, Utah 84003 USA.

Moscow Scientific and Practical Center of Sports Medicine, 105120, Moscow, Zemlyanoy Val St., 53

The ability of noni juice to improve endurance in athletes was evaluated clinically. A placebo-controlled

clinical trial with noni juice (TNJ) was conducted in 40 highly-trained athletes. Drinking 100

mL of TNJ twice daily increased endurance (time-to-fatigue) by 21%, and improved antioxidant status as measured by a 25% decrease in blood chemiluminescence. Chemical analyses by multiple laboratories and drug-urine screening of human volunteers reveal that TNJ does not contain any illegal drugs or substances prohibited by the World Anti-doping Agency. The collective results indicate that TNJ improves endurance via potent antioxidant effects. The results warrant human clinical trials to assess the dosages and the feasibility of using TNJ by athletes participating in strenuous sports such as

football, rugby, ice hockey, soccer and basketball.

 

15: Inhibition of angiogenic initiation and disruption of newly established human vascular networks by juice from Morinda citrifolia (noni)

Journal Angiogenesis

Issue Volume 6, Number 2 / June, 2003

 

Conrad A. Hornick, Amy Myers, Halina Sadowska-Krowicka, Catherine T. Anthony and Eugene A. Woltering

Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA (et. al)

 

Abstract  noni, the juice of the fruit from the Morinda citrifolia plant, has been used for centuries as a medicinal agent. We tested the effects of noni juice in a three-dimensional fibrin clot matrix model using human placental vein and human breast tumor explants as sources for angiogenic vessel development. Noni in concentrations of 5% (vol/vol) or greater was highly effective in inhibiting the initiation of new vessel sprouts from placental vein explants, compared with initiation in control explants in media supplemented with an equivalent amount of saline. These concentrations of noni were also effective in reducing the growth rate and proliferation of newly developing capillary sprouts. When used at a concentration of 10% in growth media, noni was able to induce vessel degeneration and apoptosis in wells with established capillary networks within a few days of its application. We also found that 10% noni juice in media was an effective inhibitor of capillary initiation in explants from human breast tumors. In tumor explants which did show capillary sprouting, the vessels rapidly degenerated (2–3 days) in those exposed to media supplemented with 10% noni.

 

16: Meeting Report

03/02/2006

 

Noni juice may lower total cholesterol and triglycerides in adult smokers

 

Abstract P78 (EPI)

 

PHOENIX, Ariz., March 2 – Noni, an indigenous plant of the South Pacific used in Polynesian folk medicine for over 2,000 years, may lower total cholesterol and triglycerides, according to a study reported today at the American Heart Association’s 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.

 

After one month’s use, noni juice significantly reduced cholesterol and triglycerides in current smokers with elevated cholesterol levels.

 

“We chose smokers because they tend to have higher total cholesterol levels and are at higher risk for heart disease than nonsmokers,” said Mian-Ying Wang, M.D., M.S., lead author of the study and assistant research professor at the University of Illinois College of Medicine in Rockford.

 

Previous studies found that noni juice — made from fruit of Morinda Citrifolia, (noni tree) — had strong antioxidant, anti-coagulation, anti-inflammatory and anti-cancer properties.

 

Researchers analyzed total serum cholesterol and triglyceride levels of 132 current smokers with cholesterol levels higher than 190 milligrams per deciliter (mg/dL).   The current smokers were 20 to 60 years old and were not on cholesterol-lowering medication during the study.

 

Researchers randomly assigned 13 men and 13 women to drink a juice (placebo), similar to noni in look and taste, and 57 women and 49 men to drink real noni juice that was branded Tahitian Noni® juice.   No one in the study knew which juice that they were drinking.

 

“The company formulates its noni juice with blueberry and grape juices to make it more palatable,” Wang said.  “Otherwise, due to noni’s pungent odor and taste, it would be difficult to drink.”

 

After drinking one to four ounces of the noni juice daily, noni drinkers’ average total cholesterol dropped from 235.2 mg/dL to 190.2 mg/dL, and average triglyceride levels declined from 242.5 mg/dL to 193.5 mg/dL.   The placebo group’s average total cholesterol and triglyceride levels did not significantly change.

 

The total cholesterol levels in the placebo group rose slightly, though insignificantly, from an average 239.2 mg/dL at the start of the study to 246.6 mg/dL one month later when the study ended.   Triglyceride levels in the placebo group also rose slightly, though insignificantly, from an average of 200.9 mg/dL to 210.0 mg/dL.

 

When breaking down participants’ initial total cholesterol levels into “out of range” (191 to 220 mg/dL), “high level” (221 to 299 mg/dL), and “very high level” (at or higher than 300 mg/dL), the researchers reported that total cholesterol decreased:

 

7 percent (14 mg/dL) among “out-of-range” noni drinkers

18 percent (45 mg/dL) among “high level” noni drinkers

22 percent (74 mg/dL) among “very high level” noni drinkers

They found similar drops among triglyceride levels in the noni group.

 

The study, a double-blind, placebo controlled, randomized clinical trial with men and women, was approved by the University of Illinois College (UIC) Institutional Review Board.

 

According to Wang, the results are a strong indicator that noni juice may lower total cholesterol and triglyceride levels in current smokers.   However, the study had limited participants, so the power of the study was small.

 

“In a future study, a large clinical trial in the general population should be conducted to confirm the long-term effect on total cholesterol,” Wang said.

 

Coauthors are Eric Henley, M.D.; Jeanette Nolting, Ph.D.; Alexandra Cheerva, M.D., M.S.; Jarakae Jensen, M.S.; Gary Anderson, M.D.; Diane Nowicki, M.S. and Stephen Story, B.S.

 

17. United States Patent  5,278,189

Rath ,   et al.  January 11, 1994 

--------------------------------------------------------------------------------

Prevention and treatment of occlusive cardiovascular disease with ascorbate (Vitamin C) and substances that inhibit the binding of lipoprotein (A)

Abstract

A method is provided for prevention and treatment of cardiovascular disease, such as atherosclerosis, by administering therapeutically effective dosages of a drug comprised of ascorbate (Vitamion C), lipoprotein(a) binding inhibitors, and antioxidants.

--------------------------------------------------------------------------------

Inventors:  Rath; Matthias W. (7141 Kirchberg/Murr, DE), Pauling; Linus C. (Big Sur, CA) 

Appl. No.:  07/557,516

Filed:  July 24, 1990

References:

Vitamin C in Health and Disease, Basu et al., AVI Publishing Co., Inc. (1982) pp. 95-101.

The Nutrition Desk Reference, Garrison et al, Keats Publishing Inc. (1985) pp. 172-177. .

Rath, M. & L. Pauling, "Solution of the puzzle of human cardiovascular disease: Its primary cause is ascorbate deficinecy leading to the deposition of lipoprotein(a) and fibrinogen/fibrin in the vascular wall," J. Orthomolecular Med. (In Press 1991).

Som, S. et al., "Ascorbic acid metabolism in diabetes mellitus," Metabolism 30:572-577 (1981).

 

18. Additional References

Stone, Irwin (1972). The Healing Factor: Vitamin C Against Disease. Grosset and Dunlap. ISBN 0-448-11693-6.  , Levy, Thomas E. (2002). Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins. Livon Books, p. 36. ISBN 1-4010-6963-0.,  de la Fuente M, Ferrández M, Burgos M, Soler A, Prieto A, Miquel J (1998). "Immune function in aged women is improved by ingestion of vitamins C and E". Can J Physiol Pharmacol 76 (4): 373–80

 

 

19: J Agric Food Chem. 2002 Dec 4;50(25):7449-54.

 

Antioxidant and antiproliferative activities of common fruits.

 

Sun J, Chu YF, Wu X, Liu RH.

Department of Food Science, Cornell University, Ithaca, New York 14853-7201, USA.

 

Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.

 

20: Phytochemistry. 2005 Sep;66(18):2281-91.

 

A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity.

 

Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M.

Marucci Center for Blueberry Cranberry Research, Rutgers University, Chatsworth, NJ 08019, USA. ahowell@aesop.rutgers.edu

 

Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products. The isolated A-type proanthocyanidins from cranberry juice cocktail elicited in vitro anti-adhesion activity at 60 microg/ml, the B-type proanthocyanidins from grape exhibited minor activity at 1200 microg/ml, while other B-type proanthocyanidins were not active. Anti-adhesion activity in human urine was detected following cranberry juice cocktail consumption, but not after consumption of the non-cranberry food products. Results suggest that presence of the A-type linkage in cranberry proanthocyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities and aid in maintaining urinary tract health.

 

21: Curr Opin Investig Drugs. 2008 Apr;9(4):371-8.

 

Sirtuins: novel targets for metabolic disease.

 

Elliott PJ, Jirousek M.

Sirtris Pharmaceuticals Inc, 200 Technology Square, Cambridge, MA 02139, USA. pelliott@sirtrispharma.com

 

Sirtuins represent a novel family of enzymes that are collectively well situated to help regulate nutrient sensing and utilization, metabolic rate and ultimately metabolic disease. Activation of one of these enzymes, SIRT1, leads to enhanced activity of multiple proteins, including peroxisome-proliferator activated receptor coactivator-1alpha (PGC-1alpha), which helps to mediate some of the in vitro and in vivo effects of sirtuins. As such, enhanced SIRT1 activity decreases glucose levels, improves insulin sensitivity, increases mitochondrial number and function, decreases adiposity, improves exercise tolerance and potentially lowers body weight. SRT-501 is a proprietary formulation of resveratrol with improved bioavailability. As such, SRT-501 represents the first in a novel class of SIRT1 activators that has proven to be safe and well-tolerated in humans. Clinical trials in type 2 diabetic patients are currently underway.

 

22: J Nutr. 2001 Jun;131(6):1844-9

 

Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice.

 

Kimura Y, Okuda H.

Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. yokim@m.ehime-u.ac.jp

 

Resveratrol is a naturally occurring phytoalexine found in medicinal plants. We found that resveratrol, at doses of 2.5 and 10 mg/kg, significantly reduced the tumor volume (42%), tumor weight (44%) and metastasis to the lung (56%) in mice bearing highly metastatic Lewis lung carcinoma (LLC) tumors, but not at a dose of 0.6 mg/kg. Resveratrol did not affect the number of CD4(+), CD8(+) and natural killer (NK)1.1.(+) T cells in the spleen. Therefore, the inhibitory effects of resveratrol on tumor growth and lung metastasis could not be explained by natural killer or cytotoxic T-lymphocyte activation. In addition, resveratrol inhibited DNA synthesis most strongly in LLC cells; its 50% inhibitory concentration (IC(50)) was 6.8 micromol/L. Resveratrol at 100 micromol/L increased apoptosis to 20.6 +/- 1.35% from 12.1 +/- 0.36% (P < 0.05) in LLC cells, and decreased the S phase population to 22.1 +/- 1.03% and 29.2 +/- 0.27% from 35.2 +/- 1.72% (P < 0.05) at concentrations of 50 and 100 micromol/L, respectively. Resveratrol inhibited tumor-induced neovascularization at doses of 2.5 and 10 mg/kg in an in vivo model. Moreover, resveratrol significantly inhibited the formation of capillary-like tube formation from human umbilical vein endothelial cells (HUVEC) at concentrations of 10-100 micromol/L; the degree of the inhibition of capillary-like tube formation by resveratrol was 45.5% at 10 micromol/L, 50.2% at 50 micromol/L and 52.6% at 100 micromol/L. Resveratrol inhibited the binding of vascular endothelial growth factor (VEGF) to HUVEC at concentrations of 10-100 micromol/L, but not at concentrations of 1 and 5 micromol/L. The degree of inhibition of VEGF binding to HUVEC by resveratrol was 16.9% at 10 micromol/L, 53.2% at 50 micromol/L and 47.8% at 100 micromol/L. We suggest that the antitumor and antimetastatic activities of resveratrol might be due to the inhibition of DNA synthesis in LLC cells and the inhibition of LLC-induced neovascularization and tube formation (angiogensis) of HUVEC by resveratrol.

 

 

23. Public release date: 25-Mar-2008

 

Contact: Leslie Orr

Leslie_Orr@urmc.rochester.edu

585-275-5774

University of Rochester Medical Center

 

Mounting evidence shows red wine antioxidant kills cancer

Researchers pinpoint how resveratrol induces pancreatic cancer cell death

Rochester researchers showed for the first time that a natural antioxidant found in grape skins and red wine can help destroy pancreatic cancer cells by reaching to the cell's core energy source, or mitochondria, and crippling its function. The study is published in the March edition of the journal, Advances in Experimental Medicine and Biology.

 

The study also showed that when the pancreatic cancer cells were doubly assaulted -- pre-treated with the antioxidant, resveratrol, and irradiated -- the combination induced a type of cell death called apoptosis, an important goal of cancer therapy.

 

The research has many implications for patients, said lead author Paul Okunieff, M.D., chief of Radiation Oncology at the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

 

Although red wine consumption during chemotherapy or radiation treatment has not been well studied, it is not "contraindicated," Okunieff said. In other words, if a patient already drinks red wine moderately, most physicians would not tell the patient to give it up during treatment. Perhaps a better choice, Okunieff said, would be to drink as much red or purple grape juice as desired.

 

Yet despite widespread interest in antioxidants, some physicians are concerned antioxidants might end up protecting tumors. Okunieff's study showed there is little evidence to support that fear. In fact, the research suggests resveratrol not only reaches its intended target, injuring the nexus of malignant cells, but at the same time protects normal tissue from the harmful effects of radiation.

 

"Antioxidant research is very active and very seductive right now," Okunieff said. "The challenge lies in finding the right concentration and how it works inside the cell. In this case, we've discovered an important part of that equation. Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive."

 

Resveratrol is known for its ability to protect plants from bacteria and fungi. Purified versions have been described in scientific journals as potential anti-cancer, anti-inflammatory and anti-atherogenic agents, and for their ability to modulate cell growth. Other well-known antioxidants derived from natural sources include caffeine, melatonin, flavonoids, polyphenols, and vitamins C and E.

 

A flurry of antioxidant studies in recent years has not proven how and why they work at the cellular level. At the suggestion of a young scientist in his lab, Okunieff began studying resveratrol as a tumor sensitizer. That's when they discovered its link to the mitochondria.

 

The discovery is critical because, like the cell nucleus, the mitochondria contains its own DNA and has the ability to continuously supply the cell with energy when functioning properly. Stopping the energy flow theoretically stops the cancer.

 

Researchers divided pancreatic cancer cells into two groups: cells treated without resveratrol, or with resveratrol, at a relatively high dose of 50 mg/ml, in combination with ionizing radiation. (The resveratrol concentration in red wine can be as high as 30 mg/ml, the study said, and higher doses are expected to be safe as long as a physician is monitoring.)

 

They evaluated the mitochondria function of the cells treated with resveratrol, and also measured apoptosis (cell death), the level of reactive oxygen species in the cells, and how the cell membranes responded to the antioxidant.

 

Laboratory experiments showed that resveratrol:

 

 

Reduced the function of proteins in the pancreatic cancer cell membranes that are responsible for pumping chemotherapy out of the cell, making the cells chemo-sensitive.

 

Triggered the production of reactive oxygen species (ROS), which are substances circulating in the human body that have been implicated in a number of diseases: when ROS is increased, cells burn out and die.

 

Caused apoptosis, which is likely the result of increased ROS.

 

Depolarized the mitochondrial membranes, which indicates a decrease in the cell's potential to function. Radiation alone does not injure the mitochondrial membrane as much.

 

The team also wanted to investigate why pancreatic cancer cells seem to be particularly resistant to chemotherapy. The pancreas, a gland located deep in the abdomen, produces insulin and regulates sugar, and pumps or channels powerful digestive enzymes into the duodenum. This natural pumping process, however, ends up ridding the needed chemotherapy from cells in the pancreas. But just as reseveratrol interferes with the cancer cells' energy source, it also may decrease the power available to pump chemotherapy out of the cell.

 

"While additional studies are needed," Okunieff said, "this research indicates that resveratrol has a promising future as part of the treatment for cancer."

 

In the same journal, Okunieff and his group also reviewed why resveratrol protects normal tissue, and found that antioxidants can be designed to take advantage of certain biochemical properties or cellular targets, making them more effective.

 

 

Citations:

 

Wade, Nicholas (November 16 2006). "Red Wine Ingredient Increases Endurance, Study Shows". New York Times. 

 

Cell, Vol 127, 1109–1122, 15 December 2006; Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α

 

24: B12 deficiency requires high supplement doses

WAGENINGEN, THE NETHERLANDS. Vitamin B12 deficiency is fairly common among older people and can cause anemia, pain and depression. Supplementation with cobalamin may reverse the deficiency, however, the ideal dose when given orally is yet to be determined. A team from the University of Wageningen undertook a study in which 120 participants were given either 2.5, 100, 250, 500 or 1,000ug (micrograms) of cyanocobalamin in capsules per day. These doses cover the full range from recommended dietary allowance in the Netherlands to the normal dose used in injections for B12 deficiency. The participants were aged 70 to 94, with an average age of 80. They were all mildly deficient in vitamin B12, with serum concentrations of 100 to 300 picomoles per liter. Their levels of methylmalonic acid (MMA, a marker for vitamin B12 deficiency) were above 0.26umol per liter, showing a deficiency. All of the participants received each of the experimental doses for 16 weeks, in a random order. Compliance with the medication was very high, at 98 per cent. Overall, levels of MMA and serum vitamin B12 improved with increasing doses of cobalamin. Elevated MMA was significantly reduced after 8 weeks, and remained so after 16 weeks. The percentages of participants whose MMA reduced to below 0.26umol per liter when taking 2.5, 100, 250, 500 or 1,000ug cobalamin were 21, 38, 52, 62 and 76 per cent respectively.

 

The researchers explain that a major knowledge gap existed over the lowest oral cobalamin dose required to normalize elevated MMA. They state that in this study, a daily dose of 647-1032ug was the lowest dose to give 80-90 per cent of the maximum reduction in MMA. These doses led to an average reduction in MMA of 33 per cent. However, they add that diagnosing vitamin B12 deficiency is complicated due to the limitations of current techniques. The authors conclude that the lowest dose needed to normalize vitamin B12 deficiency is more than 200 times higher than the recommended dietary allowance. They add that the relevance of treating vitamin B12 deficiency in older people could be substantial, were further trials able to show benefits to cognitive functioning and depression.

Eussen, S. J. P. M., et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency. Archives of Internal Medicine, Vol. 165, May 2005, pp.1167-1172

 

25: Effectiveness of vitamin B12 supplementation

DENVER, COLORADO. It is estimated that about 16% of older adults are vitamin B12 (cobalamin) deficient. This deficiency is mostly related to an inability to absorb cobalamin bound to food. Several experiments have shown that this problem does not affect people's ability to absorb free or synthetic cobalamin. A lack of vitamin-B12 can lead to megaloblastic anemia and, if untreated, to irreversible neurological damage that may mimic Alzheimer's disease.

There is ample evidence that injections of cobalamin can quickly correct a deficiency as can oral supplementation with 1-2 mg/day. It is not clear, however, whether smaller amounts, such as the 25 mcg or so found in multivitamins, are sufficient to correct a deficiency.

A team of researchers from the universities of Washington and Colorado has just released a study designed to determine just how much oral cobalamin supplementation is required to reverse a deficiency. The study involved 23 older patients who had been diagnosed as being vitamin B12 deficient (serum cobalamin level less than 221 pmol/L and serum methylmalonic acid [MMA] level greater than 271 nmol/l). All participants received 25 mcg/day of cobalamin during the first 6 weeks, 100 mcg/day during the next 6 weeks, and 1000 mcg/day during the final 6 weeks of the study. Two participants achieved normal MMA levels with the 25 mcg/day dose, an additional 5 with the 100 mcg/day dose, but it took 1000 mcg/day (1 mg/day) before an additional 12 regained normal MMA levels. Thus 19 out of 23 patients (83%) normalized their MMA level and eliminated their vitamin B12 deficiency at a daily intake of 1000 mcg/day. The 1000 mcg/day dose was also effective in lowering homocysteine level in 75% of the patients, but folic acid supplementation was required in 4 of the patients in order to bring homocysteine concentrations down to an acceptable level.

The researchers conclude that most cobalamin-deficient older people require more than 100 mcg/day of oral cobalamin to correct their deficiency.

Rajan, S, et al. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. Journal of the American Geriatrics Society, Vol. 50, November 2002, pp. 1789-95

 

26: A daily vitamin pill helps combat atherosclerosis

CLEVELAND, OHIO. A high blood level of the amino acid homocysteine has been linked to an increased risk of atherosclerosis and thrombosis. It is known that oral supplementation with folic acid will lower homocysteine levels to acceptable norms, but it is not clear just how much folic acid is required to achieve this effect. Now researchers at the Cleveland Clinic Foundation report that the amount of folic acid (400 micrograms) found in most multivitamin preparations is sufficient to lower homocysteine levels in heart disease patients. Their experiment involved 95 patients who had either had a heart attack or suffered from advanced atherosclerosis. The patients were divided into four groups with one group receiving 400 micrograms/day (0.4 mg/day) of folic acid, one group receiving 1 mg/day, one group receiving 5 mg/day, and the fourth group receiving a placebo. All patients receiving folic acid also received 12.5 mg of vitamin B6 per day and 500 micrograms of vitamin B12. After 90 days the plasma homocysteine levels had dropped from 13.8 to 9.6 micromol/L in the 400 micrograms/day folic acid group, from 13.0 to 9.8 micromol/L in the 1 mg/day group, and from 14.8 to 9.7 micromol/L in the 5 mg/day group. Also after 90 days the plasma levels of folic acid had risen from 28 nanomol/L in the placebo group to 63 nmol/L in the 400 micrograms/day supplement group, to 80 nmol/L in the 1 mg/day group, and to 162 nmol/L in the 5 mg/day group. Vitamin B6 levels rose from 75 nmol/L to about 250 nmol/L in the supplemented groups and vitamin B12 levels rose from about 300 picomol/L to 525 picomol/L. The researchers conclude that a daily dose of 400 micrograms of folic acid combined with vitamins B6 and B12 will normalize homocysteine levels in heart disease patients.

Lobo, Arlene, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. American Journal of Cardiology, Vol. 83, March 15, 1999, pp. 821- 25

 

27: Vitamin B-12 increases efficiency of folic acid

BONN, GERMANY. There is increasing evidence that high blood levels of the amino acid homocysteine increases the risk of vascular disease, coronary heart disease, neural tube defects, and Alzheimer's disease. Folic acid supplementation is known to lower homocysteine levels and laws have recently been passed in the United States mandating folic acid fortification of bread and cereal. Now researchers at the University of Bonn report that folic acid's homocysteine lowering capacity can be markedly increased by also supplementing with vitamin B-12 (cobalamin). Their study involved 150 young, healthy women (average age of 24 years) who after a four-week washout period were randomized into three groups. Group 1 received a daily supplement of 400 micrograms of folic acid, group 2 received 400 micrograms/day of folic acid and 6 micrograms/day of vitamin B-12, and group 3 received 400 micrograms/day of folic acid and 400 micrograms/day of vitamin B-12. After four weeks the average concentration of plasma homocysteine had dropped by 11 per cent in group 1, 15 per cent in group 2, and 18 per cent in group 3. The researchers noted that study participants with high initial homocysteine concentrations benefited more from supplementation than did women with lower initial homocysteine levels. It was also noted that vitamin B-12 levels increased significantly over the four-week period in the women whose supplements included vitamin B-12. This provides further proof that oral vitamin B-12 is indeed adequately absorbed. The researchers conclude that the benefits of folate supplementation can be markedly enhanced by the addition of vitamin B-12. They point out that vitamin B-12 deficiency is widespread especially among the elderly. The addition of vitamin B-12 to folic acid supplements also prevents the possibility that supplementation with just folic acid could mask pernicious anaemia resulting from a vitamin B-12 deficiency which in turn may lead to irreversible nerve damage.

Bronstrup, Anja, et al. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. American Journal of Clinical Nutrition, Vol. 68, November 1998, pp. 1104-10

 

28: Folic acid helps prevent coronary heart disease

SEATTLE, WASHINGTON. A high level of homocysteine in the blood has been clearly implicated in heart disease, stroke and peripheral vascular disease. Homocysteine is an amino acid that is not found in protein as such, but is involved in the metabolism of other amino acids (methionine and cysteine). The average blood level of total homocysteine in male adults is about 10 micromol/L. Now researchers at the University of Washington confirm that people with a higher than normal level of homocysteine have a greater risk of developing vascular disease. The researchers evaluated 17 studies dealing with the link between homocysteine levels and the risk of coronary artery disease (CAD). They found that men with a level of 15 micromol/L had a 60 per cent greater risk of developing CAD while the increased risk for women was 80 per cent. The risk for cerebrovascular disease (stroke) was found to be almost twice as high in men and women with elevated (15 micromol/L) homocysteine levels. The risk of developing peripheral vascular disease (e.g. intermittent claudication) was found to be almost seven times higher among people with elevated homocysteine levels. The researchers conclude that a high homocysteine level is an independent risk factor for vascular disease and that a 5 micromol/L elevation results in the same increase in CAD risk as a cholesterol increase of 0.5 mmol/L (20 mg/dL).

 

The researchers also evaluated 12 studies concerning the connection between dietary intake of folic acid and homocysteine level. They found that folic acid is very effective in lowering homocysteine levels. An intake of 400 micrograms per day (the level found in most supplements) lowers the homocysteine level by about 6 micromol/L. The researchers conclude that over 44,000 lives could be saved every year if just half the population of the United States were to supplement with 400 micrograms per day of folic acid. Unfortunately, recent surveys have shown that 88 per cent of American adults have a daily intake of folic acid below 400 micrograms. The researchers warn that an increased intake of folic acid may mask a vitamin B-12 deficiency and recommend that 1 mg of vitamin B-12 be added to all supplements containing 400 micrograms of folic acid. They also recommend that consideration be given to fortifying grain products with 350 micrograms of folic acid per 100 grams of grains. This strategy would have the added advantage of making it easier to prevent neural tube defects in newborn babies.

Boushey, Carol J., et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Journal of the American Medical Association, Vol. 274, No. 13, October 4, 1995, pp. 1049- 57