Life Extension Magazine®

Issue: Jul 2013


Cancer chemoprevention by pomegranate: laboratory and clinical evidence.

Pomegranate fruit from the tree Punica granatum has been dubbed as the “nature’s power fruit.” Dating back to Biblical times, the tree itself is attributed to possess extraordinary medicinal properties. The geographical distribution of the tree, being native to the Middle East and some Asian countries, is generally attributed to a lack of interest in its medicinal properties by many western scientists. However, the unique biochemical composition of the pomegranate fruit being rich in antioxidant tannins and flavonoids has recently drawn attention of many investigators to study its exceptional healing qualities. Recent research has shown that pomegranate extracts selectively inhibit the growth of breast, prostate, colon and lung cancer cells in culture. In preclinical animal studies, oral consumption of pomegranate extract inhibited growth of lung, skin, colon and prostate tumors. An initial phase II clinical trial of pomegranate juice in patients with prostate cancer reported significant prolongation of prostate specific antigen doubling time. This review focuses on recent investigations into the effects of pomegranate fruit on cancer.

Nutr Cancer. 2009;61(6):811-5

Comparative effects of dried plum and dried apple on bone in postmenopausal women.

Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among the nutritional factors, dried plum or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. The objective of the present study was to examine the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. We recruited 236 women, 1-10 years postmenopausal, not on hormone replacement therapy or any other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of the two treatment groups: dried plum (100 g/d) or dried apple (comparative control). Participants received 500 mg Ca plus 400 IU (10 µg) vitamin D daily. Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline, 3, 6 and 12 months to assess bone biomarkers. Physical activity recall and 1-week FFQ were obtained at baseline, 3, 6 and 12 months to examine physical activity and dietary confounders as potential covariates. Dried plum significantly increased BMD of ulna and spine in comparison with dried apple. In comparison with corresponding baseline values, only dried plum significantly decreased serum levels of bone turnover markers including bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b. The findings of the present study confirmed the ability of dried plum in improving BMD in postmenopausal women in part due to suppressing the rate of bone turnover.

Br J Nutr. 2011 Sep;106(6):923-30

Pilot study of oral anthocyanins for colorectal cancer chemoprevention.

Naturally occurring anthocyanins possess colorectal cancer chemopreventive properties in rodent models. We investigated whether mirtocyan, an anthocyanin-rich standardized bilberry extract, causes pharmacodynamic changes consistent with chemopreventive efficacy and generates measurable levels of anthocyanins in blood, urine, and target tissue. Twenty-five colorectal cancer patients scheduled to undergo resection of primary tumor or liver metastases received mirtocyan 1.4, 2.8, or 5.6 grams (containing 0.5-2.0 grams anthocyanins) daily for 7 days before surgery. Bilberry anthocyanins were analyzed by high performance liquid chromatography (HPLC) with visible or mass spectrometric detection. Proliferation was determined by immunohistochemistry of Ki-67 in colorectal tumor. Concentrations of insulin-like growth factor (IGF)-I were measured in plasma. Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in plasma, colorectal tissue, and urine, but not in liver. Anthocyanin concentrations in plasma and urine were roughly dose-dependent, reaching approximately 179 ng/gram in tumor tissue at the highest dose. In tumor tissue from all patients on mirtocyan, proliferation was decreased by 7% compared with preintervention values. The low dose caused a small but nonsignificant reduction in circulating IGF-I concentrations. In conclusion, repeated administration of bilberry anthocyanins exerts pharmacodynamic effects and generates concentrations of anthocyanins in humans resembling those seen in Apc(Min) mice, a model of FAP adenomas sensitive to the chemopreventive properties of anthocyanins. Studies of doses containing <0.5 gram bilberry anthocyanins are necessary to adjudge whether they may be appropriate for development as colorectal cancer chemopreventive agents.

Cancer Prev Res (Phila). 2009 Jul;2(7):625-33

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

BACKGROUND: Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. METHODS: Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-kb and CPT1 in the heart and the liver were characterised. RESULTS: High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-kb and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-kb and CPT1. CONCLUSIONS: Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

Eur J Nutr.2012 Apr 27

The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis.

Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. Thus, in this study, we investigated the anti-diabetic and anti-oxidative effects of anthocyanins (ANT) from black soybean seed coats in streptozotocin (STZ)-induced diabetic rats. The administration of ANT markedly decreased glucose levels and improved heart hemodynamic function (left ventricular end diastolic pressure, +/-dp/dt parameters). ANT not only enhanced STZ-mediated insulin level decreases, but also decreased the triglyceride levels induced by STZ injection in serum. Diabetic rats exhibited a lower expression of glucose transporter 4 proteins in the membrane fractions of heart and skeletal muscle tissues, which was enhanced by ANT. In addition, ANT activated insulin receptor phosphorylation, suggesting an increased utilization of glucose by tissues. Moreover, ANT protected pancreatic tissue from STZ-induced apoptosis through regulation of caspase-3, Bax, and Bcl-2 proteins. Furthermore, ANT significantly suppressed malondialdehyde levels and restored superoxide dismutase and catalase activities in diabetic rats. Interestingly, the observed effects of ANT were superior to those of glibenclamide. Taken together, ANT from black soybean seed coat have anti-diabetic effects that are due, in part, to the regulation of glucose transporter 4 and prevention of insulin resistance and pancreatic apoptosis, suggesting a possible use as a drug to regulate diabetes.

Mol Nutr Food Res. 2009 Nov;53(11):1419-29

Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties.

Studies suggest that consumption of berry fruits, including strawberries (Fragaria x ananassa Duch.), may have beneficial effects against oxidative stress mediated diseases such as cancer. Berries contain multiple phenolic compounds, which are thought to contribute to their biological properties. Comprehensive profiling of phenolics from strawberries was previously reported using high-performance liquid chromatography with mass spectrometry (HPLC-MS) detection. The current study reports the isolation and structural characterization of 10 phenolic compounds from strawberry extracts using a combination of Amberlite XAD16-resin and C18 columns, HPLC-UV, and nuclear magnetic resonance (NMR) spectroscopy methods. The phenolics were cyanidin-3-glucoside ( 1), pelargonidin (2), pelargonidin-3-glucoside (3), pelargonidin-3-rutinoside (4), kaempferol (5), quercetin (6), kaempferol-3-(6’-coumaroyl)glucoside) (7), 3,4,5-trihydroxyphenyl-acrylic acid (8), glucose ester of ( E)- p-coumaric acid (9), and ellagic acid . Strawberry crude extracts and purified compounds 1- 10 were evaluated for antioxidant and human cancer cell antiproliferative activities by the Trolox equivalent antioxidant capacity (TEAC) and luminescent ATP cell viability assays, respectively. Among the pure compounds, the anthocyanins 1 (7,156 microM Trolox/mg), 2 (4,922 microM Trolox/mg), and 4 (5,514 microM Trolox/mg) were the most potent antioxidants. Crude extracts (250 microg/mL) and pure compounds (100 microg/mL) inhibited the growth of human oral (CAL-27, KB), colon (HT29, HCT-116), and prostate (LNCaP, DU145) cancer cells with different sensitivities observed between cell lines. This study adds to the growing body of data supporting the bioactivities of berry fruit phenolics and their potential impact on human health.

J Agric Food Chem. 2008 Feb 13;56(3):670-5

Multiple berry types preventN-nitrosomethylbenzylamine-induced esophageal cancer in rats.

PURPOSE: The present study compared the ability of different berry types to prevent chemically-induced tumorigenesis in the rat esophagus. We also determined if berries influence the levels of inflammatory cytokines in the serum of carcinogen-treated rats. METHODS: Rats were treated with the carcinogen N-nitrosomethylbenzylamine (NMBA) for 5 weeks, then placed on diets containing 5% of either black or red raspberries, strawberries, blueberries, noni, açaí or wolfberry until the end of the study. The effects of the berries on tumor incidence, multiplicity and size were determined, as well as their effects on the levels of selected inflammatory cytokines in serum. RESULTS: All berry types were about equally effective in inhibiting NMBA-induced tumorigenesis in the rat esophagus. They also reduced the levels of the serum cytokines, interleukin 5 (IL-5) and GRO/KC, the rat homologue for human interleukin-8 (IL-8), and this was associated with increased serum antioxidant capacity. CONCLUSIONS: Seven berry types were about equally capable of inhibiting tumor progression in the rat esophagus in spite of known differences in levels of anthocyanins and ellagitannins. Serum levels of IL-5 and GRO/KC (IL-8) may be predictive of the inhibitory effect of chemopreventive agents on rat esophageal carcinogenesis.

Pharm Res.2010 Jun;27(6):1138-45

Effect of the novel radiant zone drying method on anthocyanins and phenolics of three blueberry liquids.

The Radiant Zone dryer (RZD) is a novel drying method designed to dry liquid food products into powders. The impact of RZD on the phytochemical content of three blueberry liquid products (extract, juice, and puree) was examined. Comparative analysis between liquid and dried products revealed no statistically significant changes in the total anthocyanins (extract liquid/powder, 11.7/11.2 mg/g of dry weight; juice liquid/powder, 2.7/2.5 mg/g of dry weight; puree liquid/powder, 1.7/1.6 mg/g of dry weight, quantified as cyanidin 3-glucoside equivalents) and total phenolics (extract liquid/powder, 97.1/113.1 mg/g of dry weight; juice liquid/powder, 16.6/17.4 mg/g of dry weight; puree liquid/powder, 8.3/6.2 mg/g of dry weight, quantified as gallic acid equivalents). Total antioxidant activity also showed no significant variation between wet and dried products. The high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis of the products exhibited a similar profile of 13 glycosylated anthocyanins. This study demonstrates that the novel RZD produces high-quality products because the retention of anthocyanins and phenolics during dehydration using RZD is the same as that for freeze drying. The RZD method of operation and its advantages over other dryers is also discussed.

J Agric Food Chem.2010 Jan 13;58(1):324-30

Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet.

Male C57BL/6 mice received diets with either 10% of kcal from fat, or a high fat diet [45% (HF45) or 60% (HF60) kcal from fat]. Diets were prepared with or without freeze-dried powders (10%) from whole blueberries (BB), strawberries (SB), Concord grape or black raspberry. In the 2nd study, purified anthocyanins (ACNs) from SB or BB were added to the drinking water of the treatments fed the HF60 diet. In Study 1, serum triglycerides were increased by feeding the HF45 diet but were elevated further when black raspberry or BB was included in the HF45 diet. Liver total lipids and triglycerides were increased in mice fed HF45 diet and inclusion of any of the berry powders in the HF45 diet did not alter concentrations compared to HF45 controls. In the 2nd study, mice fed the HF60 diet plus purified ACNs from BB in the water had lower body weight gains and body fat than the HF60 fed. Serum cholesterol and triglyceride levels were elevated with the HF60 diet and decreased to control levels when ACNs from either SB or BB were included in the drinking water. Serum leptin levels were consistently decreased to control low fat levels in those ACN treatments in which measures of body fat were decreased. Administering purified ACNs from BB and strawberry via drinking water prevented the development of dyslipidemia and obesity in mice, but feeding diets containing whole berries or purple corn (PC) ACNs did not alter the development of obesity.

Mol Nutr Food Res. 2009 Nov;53(11):1406-18

Strawberry anthocyanin and its association with postprandial inflammation and insulin.

The present study investigates the effect of strawberry antioxidants in beverage form on meal-induced postprandial inflammatory and insulin responses in human subjects. Overweight adults (n 24) consumed a high-carbohydrate, moderate-fat meal (HCFM) accompanied by either a strawberry or a placebo beverage in a cross-over design. Postprandial changes in plasma anthocyanins, their metabolites, insulin, glucose and inflammatory markers were assessed for 6 h. The postprandial concentrations of pelargonidin sulfate and pelargonidin-3-O-glucoside were significantly increased when the strawberry beverage was consumed concurrently with the HCFM compared with the placebo beverage (P < 0·001). The strawberry beverage significantly attenuated the postprandial inflammatory response as measured by high-sensitivity C-reactive protein and IL-6 (P < 0·05) induced by the HCFM. It was also associated with a reduction in postprandial insulin response (P < 0·05). Collectively, these data provide evidence for favourable effects of strawberry antioxidants on postprandial inflammation and insulin sensitivity.

Br J Nutr.2011 Sep;106(6):913-22

Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota.

OBJECTIVE: To identify the change in the incidence of cutaneous melanoma over time among young adults. PATIENTS AND METHODS: Using Rochester Epidemiology Project data, we identified patients aged 18 to 39 years who had a first lifetime diagnosis of melanoma from January 1, 1970, through December 31, 2009, in Olmsted County, Minnesota. Demographic and clinical information, including survival, was abstracted, and estimates of the incidence of melanoma and overall and disease-specific survival were generated. RESULTS: From 1970 to 2009, the incidence of melanoma increased by 8-fold among young women and 4-fold among young men. Overall and disease-specific survival seemed to improve over time; hazard ratios comparing year of diagnosis with mortality were 0.92 and 0.91, respectively. CONCLUSION: The incidence of cutaneous melanoma among young adults is rapidly increasing, especially among women. Continued close monitoring of this high-risk population is necessary.

Mayo Clin Proc. 2012 Apr;87(4):328-34

Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent.

Photoprotection is essential to prevent the deleterious effects of ultraviolet (UV) light, including skin cancer, photoaging and immunosuppression. Photoprotective agents can be classified according to their main mechanism of action. Some of them absorb or deflect UV photons (sunscreens), whereas others prevent or fix the deleterious effects of UV exposure. Here, we review recent evidence on the cellular and molecular mechanisms underlying the photoprotective effect of a Polypodium leucotomos fern extract (PL). PL is a natural mixture of phytochemicals endowed with powerful antioxidant properties. Its short-term effects include inhibition of reactive oxygen species production induced by UV radiation, DNA damage, isomerization and decomposition of trans-urocanic acid, prevention of UV-mediated apoptosis and necrosis, as well as degradative matrix remodeling, which is the main cause of photoaging. These short-term effects translate into long-term prevention of photoaging and photocarcinogenesis. A striking property is that PL can exert its effect when administered orally. Together, these effects postulate PL as a natural photoprotective agent and a potential adjuvant to phototherapy for various skin diseases.

Photochem Photobiol Sci. 2010 Apr;9(4):559-63

Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice.

A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties.

Exp Dermatol. 2012 Aug;21(8):638-40

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin—a case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. METHODS: A case-control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. RESULTS: A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥ 3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. CONCLUSIONS: Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.

BMC Cancer. 2012 Sep 20;12:417

Oral polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatoses.

AIM: Idiopathic photodermatoses (IP) are a recurrent, acquired sunlight-induced rash of delayed onset, appearing after exposure to ultraviolet radiation in susceptible individuals. The aim of this study was to assess the photoprotective activity of polypodium leucotomos (PL) in IP. METHODS: Fifty-seven patients affected by IP were recruited for the study (53 with polymorphic light eruption and 4 with solar urticaria). The use of UV protection filters or other drugs that could in some way interfere with exposure to light were excluded. All patients exposed themselves to sunlight while consuming 480 mg/day of PL extract orally. A statistical evaluation of the basal clinical conditions compared to those after sunlight exposure with PL was performed. RESULTS: About 73.68% of the patients had a benefit from the administered PL, with a significant reduction of skin reaction and subjective symptoms. No side effects were observed. Results were statistically significant (P<0.05). CONCLUSION: PL complete absence of toxicity combined with its multifactorial protection, makes it an effective and safe treatment for photoprotection in IP.

G Ital Dermatol Venereol. 2011 Apr;146(2):85-7

Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells.

The extracellular matrix (ECM) that gives tissue its structural integrity is remodeled in skin aging/photoaging and cancer via the increased expression/activities of matrixmetalloproteinases (MMP), inhibition of the tissue inhibitors of matrix metalloproteinases (TIMP), or inhibition of collagen synthesis. Transforming growth factor-beta (TGF-beta), a predominant regulator of the ECM, is inhibited in aging/photoaging and stimulated in carcinogenesis. P. leucotomos (fern) extract has potential to counteract these alterations via its antioxidant, anti-inflammatory and photoprotective properties. The goal of this research was to determine the efficacy of P. leucotomos to (a) directly inhibit MMP-1, 2, 3, and 9 activities, (b) inhibit MMP-2, and stimulate TIMPs, fibrillar collagens and TGF-beta in non-irradiated or ultraviolet (UV) radiated fibroblasts, and (c) inhibit MMPs and TGF-beta, and stimulate TIMPs in melanoma cells. To this purpose, we examined the direct effect of P. leucotomos (0-1%) on MMPs’ activities, and its effects on the expression (protein and/or transcription levels) of (1) MMPs and TIMPs in dermal fibroblasts, and melanoma cells, (2) TGF-beta in non-irradiated, UVA (2.5 J/cm2) or UVB (2.5 mJ/cm2) irradiated fibroblasts, and melanoma cells, and (3) types I, III, and V collagen in non-irradiated or UV irradiated fibroblasts. P. leucotomos directly inhibited the activities of MMPs as well as the expression of MMPs in fibroblasts, and melanoma cells while stimulating the expression of TIMPs in these cells. P. leucotomos stimulated types I, III, and V collagen in non-irradiated fibroblasts, and types I and V collagen in UV radiated fibroblasts. P. leucotomos had predominant stimulatory effects on TGF-beta expression in non-irradiated or UV radiated fibroblasts, and inhibited TGF-beta expression in melanoma cells. The effects of P. leucotomos were largely similar to that of ascorbic acid. P. leucotomos demonstrated dual protective effects on the ECM via its inhibition of the ECM proteolytic enzymes and the stimulation of the structural ECM collagens. The effects of P. leucotomos on fibroblasts and melanoma cells may be partly via its cell-specific regulation of TGF-beta expression and partly via its antioxidant property. The intake or topical application of P. leucotomos may be beneficial to skin health, in aging and cancer prevention or treatment.

Arch Dermatol Res. 2009 Aug;301(7):487-95

Polypodium leucotomos extract inhibits glutathione oxidation and prevents Langerhans cell depletion induced by UVB/UVA radiation in a hairless rat model.

In this report, we have addressed the effect of oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL) on the deleterious effects of ultraviolet radiation (UVR) on the levels of epidermal and plasmatic antioxidants in hairless rats. We have found that pretreatment with PL effectively reduced glutathione oxidation in both blood and epidermis, suggesting a potent systemic antioxidant effect. In addition, PL inhibited UVR-mediated Langerhans cell (LC) depletion. Our results demonstrate the efficacy of PL as an oral antioxidant and photoimmunoprotective agent and support its employment as a complement to topical sunscreens.

Exp Dermatol. 2008 Aug;17(8):653-8

Antiinflammatory effects of a red orange extract in human keratinocytes treated with interferon-gamma and histamine.

Red oranges are an important component of the so-called Mediterranean diet and they have been used by traditional medicine for their health protective properties, particularly to heal sore throat and cough, suggesting an interesting antiinflammatory activity. The purpose of this study was to evaluate the antiinflammatory activity of a red orange (Citrus sinensis varieties: Moro, Tarocco, Sanguinello) complex (ROC), characterized by high levels of anthocyanins, flavanones, hydroxycinnamic acids and ascorbic acid, on the human keratinocyte line NCTC 2544 exposed to interferon-gamma (IFN-gamma) and histamine. The expression of immunomodulatory membrane molecules such as inter-cellular adhesion molecule-1 (ICAM-1) by Western blot analysis, and the release of chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) through ELISA kits, were determined. ICAM-1 modulates the permanence and activation of T lymphocytes in the epidermis. MCP-1 is a specific chemoattractant for monocytes and dendritic cells. IL-8 is important for the recruitment of both neutrophils and T lymphocytes. Addition of ROC at different concentrations together with IFN-gamma and histamine induced a dose-dependent inhibition of ICAM-1 expression and MCP-1 and IL-8 release. ROC shows interesting antiinflammatory properties in human keratinocyte cells NCTC 2544. This natural complex could have a topical employment and mitigate the consequences of some skin pathologies.

Phytother Res. 2010 Mar;24(3):414-8

Involvement of inducible nitric oxide synthase and cyclooxygenase-2 in the anti-inflammatory effects of a red orange extract in human chondrocytes.

In the present study, a complex of compounds (red orange complex, ROC), obtained from three red orange varieties (Citrus sinensis varieties: Moro, Tarocco and Sanguinello), containing cyanidin glycosides, hydroxycinnamic acids, flavanone glycosides and ascorbic acid, was screened to discover new lead compounds in the suppression of the production of key molecules released during inflammatory events in interleukin-1beta (IL-beta) stimulated human primary chondrocytes. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX)-2 and intercellular adhesion molecule-1 (ICAM-1), and the release of nitric oxide, prostaglandin (PG)E(2) and interleukin-8 (IL-8) were determined. Indomethacin was used as an anti-inflammatory drug reference. ROC acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of PGE(2) and nitrite in human chondrocytes. In addition, ROC induces a significant decrease in ICAM expression and IL-8 release. These findings suggest that ROC exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression.

Nat Prod Res. 2010 Sep;24(15):1469-80

Protective effects of a red orange extract on UVB-induced damage in human keratinocytes.

UV light is considered one of the major etiological factor in skin aging, cancer and also to systemic impairment such as immunosuppression. Increased production of reactive oxygen species (ROS) and oxidative stress condition are known to play a central role in initiating and driving the signalling events that lead to cellular response following UV irradiation. In the present study we have investigated the photoprotective activity of a standardized extract from red orange (ROE), obtained from three red orange varieties and containing as main active principles phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) and ascorbic acid. The aim of this study was to evaluate the efficacy of ROE in modulating cellular responses to UVB in human keratinocytes (HaCaT). Our data indicate that ROE is potentially able to efficiently counteract UVB-induced response, and in particular some events associated to inflammation and apoptosis, such as NF-kB and AP-1 translocation and procaspase-3 cleavage. This activity is probably due to a block of cellular oxidative stress-related events. Thus we can propose ROE as a useful natural standardised extract in skin photoprotection with promising applications in the field of dermatology.

Biofactors. 2007;30(2):129-38

Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial.

Depression is a serious disorder in today’s society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo-controlled and randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double-blind, placebo-controlled, single-centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.

Phytother Res. 2005 Feb;19(2):148-51

Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial.

Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world’s most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.

J Ethnopharmacol. 2005 Feb 28;97(2):281-4

Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16-week, randomized and placebo-controlled trial.

WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer’s disease (AD). OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events. WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for.

J Clin Pharm Ther. 2010 Oct;35(5):581-8

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease.

RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer’s disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer’s Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer’s disease.

Psychopharmacology (Berl). 2010 Jan;207(4): 637-43

Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety.

Crocus sativus L. is a plant cultivated in various parts of the world. Crocins are among the active components of Crocus sativus L. The present study was designed to investigate in the rat whether or not crocins possess anxiolytic properties. For this aim, the light/dark test was selected. Either crocins, at a dose which did not influence animals’ motor activity (50mg/kg), or diazepam (1.5 mg/kg), significantly increased the latency to enter the dark compartment and prolonged the time spent in the lit chamber in the rats. Conversely, lower doses of crocins (15-30 mg/kg) did not substantially modify animals’ behaviour. The present results indicate that treatment with these active constituents of Crocus sativus L. induce anxiolytic-like effects in the rat.

Phytomedicine. 2008 Dec;15(12):1135-9

Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice.

Saffron stigma (Crocus sativus L.) is used for insomnia and anxiety in traditional medicine. In this study, the anxiolytic and hypnotic effects of saffron aqueous extract and its constituents, crocin and safranal, were studied in mice. Agents were administered intraperitoneally in mice before the experiments for the evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus maze test), locomotor activity (open field test) and motor coordination (Rotarod test). The aqueous extract reduced the locomotor activity dose dependently. At low doses, saffron showed a significant increase in the time on the open arms of the maze. When using the Rotarod method, the aqueous extract showed considerable effect on motor coordination of the mice. In the hypnotic test, only a dose of 0.56 g/kg of saffron increased the total sleep. Crocin showed no anxiolytic, hypnotic or myorelaxation effects. Safranal, in higher doses, 0.15 and 0.35 mL/kg, showed anxiolytic effects. Safranal increased the total sleep time dose dependently. This constituent at lower doses (0.05 and 0.15 mL/kg) decreased some locomotion activity parameters. Safranal demonstrated no effects on motor coordination. The results showed that saffron aqueous extract and safranal have anxiolytic and hypnotic effects.

Phytother Res. 2009 Jun;23(6):768-74

Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder.

Crocins are among the active components of the plant Crocus Sativus L. C. Sativus L. and its constituents were effective in different models of psychiatric disorders including anxiety and depression. Obsessive-compulsive disorder (OCD) is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The non selective serotonin (5-HT) receptor agonist mCPP is known to induce OCD-like behavior (excessive self-grooming) in rodents and exacerbate symptoms in patients with OCD. The present study investigated whether or not crocins were able to counteract excessive self-grooming induced by mCPP (0.6 mg/kg, i.p.) in rats. Crocins (30 and 50 mg/kg, i.p.) attenuated mCPP-induced excessive self-grooming. The present results also indicate that these effects of crocins on an animal model of OCD cannot be attributed to changes in locomotor activity. Our findings suggest that the active constituents of C. Sativus L. crocins might play a role in compulsive behavior and support a functional interaction between crocins and the serotonergic system.

Neurosci Lett. 2012 Oct 18;528(1):27-30

Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women.

Snacking is an uncontrolled eating behavior, predisposing weight gain and obesity. It primarily affects the female population and is frequently associated with stress. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. Healthy, mildly overweight women (N = 60) participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Snacking frequency, the main secondary variable, was assessed by daily self-recording of episodes by the subjects in a nutrition diary. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day (n = 31) or a matching placebo (n = 29). Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks (P < .01). The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group (P < .05). Other anthropometric dimensions and vital signs remained almost unchanged in both groups. No subject withdrawal attributable to a product effect was reported throughout the trial, suggesting a good tolerability to Satiereal. Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss. The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective.

Nutr Res. 2010 May;30(5):305-13

Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study.

OBJECTIVE: Saffron (Crocus sativus L.) has shown beneficial aphrodisiac effects in some animal and human studies. The aim of the present study was to assess the safety and efficacy of saffron on selective serotonin reuptake inhibitor-induced sexual dysfunction in women. METHODS: This was a randomized double-blind placebo-controlled study. Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study. The patients were randomly assigned to saffron (30 mg/daily) or placebo for 4 weeks. Measurement was performed at baseline, week 2, and week 4 using the Female Sexual Function Index (FSFI). Side effects were systematically recorded. RESULTS: Thirty-four women had at least one post-baseline measurement and completed the study. Two-factor repeated measure analysis of variance showed significant effect of time × treatment interaction [Greenhouse-Geisser’s corrected: F(1.580, 50.567) = 5.366, p = 0.012] and treatment for FSFI total score [F(1, 32) = 4.243, p = 0.048]. At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains of FSFI but not in desire (p = 0.196), satisfaction (p = 0.206), and orgasm (p = 0.354) domains. Frequency of side effects was similar between the two groups. CONCLUSIONS: It seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal, lubrication, and pain.

Hum Psychopharmacol. 2013 Jan;28(1):54-60

Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: a pilot study.

In this study, the effect of Crocus sativus (saffron) was studied on male erectile dysfunction (ED). Twenty male patients with ED were followed for ten days in which each morning they took a tablet containing 200mg of saffron. Patients underwent the nocturnal penile tumescence (NPT) test and the international index of erectile function questionnaire (IIEF-15) at the start of the treatment and at the end of the ten days. After the ten days of taking saffron there was a statistically significant improvement in tip rigidity and tip tumescence as well as base rigidity and base tumescence. ILEF-15 total scores were significantly higher in patients after saffron treatment (before treatment 22.15+/-1.44; after treatment 39.20+/-1.90, p<0.001). Saffron showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with ED even only after taking it for ten days.

Phytomedicine. 2009 Aug;16(8):690-3

Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.).

Since cancer is the most common cause of death in the world population, the possibility that readily available natural substances from plants, vegetables, herbs, and spices may be beneficial in the prevention of cancer warrants closer examination. Saffron in filaments is the dried, dark red stigmata of Crocus sativus L. flowers and it is used as a spice, food colorant, and a drug in medicine. A growing body of research has demonstrated that saffron extract itself and its main constituents, the carotenoids, possess chemopreventive properties against cancer. This review discusses recent literature data and our results on the cancer chemopreventive activities of saffron and its main ingredients.

Exp Biol Med (Maywood). 2002 Jan;227(1):20-5

Starch with a slow digestion property produced by altering its chain length, branch density, and crystalline structure.

The hypothesis of increasing the branch density of starch to reduce its digestion rate through partial shortening of amylopectin exterior chains and the length of amylose was investigated. Starch products prepared using beta-amylase, beta-amylase and transglucosidase, maltogenic alpha-amylase, and maltogenic alpha-amylase and transglucosidase showed significant reduction of rapidly digested starch by 14.5%, 29.0%, 19.8%, and 31.0% with a concomitant increase of slowly digested starch by 9.0%, 19.7%, 5.7%, and 11.0%, respectively. The resistant starch content increased from 5.1% to 13.5% in treated starches. The total contents of the prebiotics isomaltose, isomaltotriose, and panose (Isomaltooligosaccharides) were 2.3% and 5.5%, respectively, for beta-amylase/transglucosidase- and maltogenic alpha-amylase/transglucosidase-treated starches. The molecular weight distribution of enzyme-treated starches and their debranched chain length distributions, analyzed using high-performance size-exclusion chromatography with multiangle laser light scattering and refractive index detection (HPSEC-MALLS-RI) and HPSEC-RI, showed distinctly different patterns among starches with different enzyme treatments. A larger proportion of low molecular weight fractions appeared in starches treated additionally with transglucosidase. All enzyme-treated starches showed a mixture of B- and V-type X-ray diffraction patterns, and 1H NMR spectra showed a significant increase of alpha-1,6 linkages. Both the increase of the starch branch density and the crystalline structure in the treated starches likely contribute to their slow digestion property.

J Agric Food Chem. 2007 May 30;55(11):4540-7

Supplementing transglucosidase with a high-fiber diet for prevention of postprandial hyperglycemia in streptozotocin-induced diabetic dogs.

Indigestible oligosaccharides have been shown to normalize blood glucose and insulin concentration thereby promoting good health and preventing diseases, such as diabetes. Transglucosidase (TG, alpha-glucosidase, enzyme code (EC) is an enzyme capable of converting starch to oligosaccharides, such as iso-malto-oligosaccharides from maltose, via the action of amylase. The aim of this study was to evaluate whether oral administration of TG with maltose or dextrin is capable of reducing post-prandial serum glucose concentration in experimentally streptozotocin (STZ)-induced diabetic dogs fed on a high-fiber diet. Five healthy and five STZ-induced diabetic dogs were employed in this study. TG supplementation with dextrin or maltose had no detrimental effect in healthy dogs. In fact, TG and dextrin exhibited a flatlined serum glucose pattern, while reducing mean post-prandial serum insulin and glucose concentration as compared to control diet alone. When TG supplementation was tested in STZ-induced diabetic dogs under the context of a high fiber diet, a 13.8% and 23.9% reduction in mean glucose concentration for TG with maltose and dextrin, respectively was observed. Moreover, TG with dextrin resulted in a 13% lower mean post-prandial glucose concentration than TG with maltose, suggesting that dextrin may be a more efficient substrate than maltose when used at the same concentration (1 g/kg). Our results indicate that TG supplementation with diet can lead to lower postprandial glucose levels versus diet alone. However, the efficacy of TG supplementation may depend on the type of diet it is supplemented with. As such, TG administration may be useful for preventing the progression of diabetes mellitus and in its management in dogs.

Vet Res Commun. 2010 Feb;34(2):161-72

Effects of transglucosidase on diabetes, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial.

In this 12-week, randomized, double-blind, placebo-controlled trial, the efficacy and safety of transglucosidase (TGD) were compared with placebo in patients with type 2 diabetes mellitus (T2DM). At 12 weeks, TGD 300 mg/day and TGD 900 mg/day significantly reduced HbA1c (0.18 and 0.21%) and insulin concentration (19.4 and 25.0 pmol/l), respectively, vs. placebo. TGD 300 mg/day and TGD 900 mg/day also significantly reduced low-density lipoprotein cholesterol (0.22 and 0.17 mmol/l, respectively). TGD 900 mg/day significantly reduced triglyceride by 0.24 mmol/l and diastolic blood pressure by 8 mmHg. Placebo was associated with a significant increase from baseline in body mass index, alanine aminotransferase and aspartate aminotransferase (0.17 kg/m(2) , 3 and 2 U/l, respectively), whereas TGD was not. TGD 300 mg/day significantly increased high-molecular-weight adiponectin by 0.6 µg/ml. Adverse events did not differ significantly between the groups. TGD resulted in lowering of HbA1c and blood insulin level and improvements in metabolic and cardiovascular risk factors in T2DM.

Diabetes Obes Metab. 2012 Apr;14(4):379-82

Action of transglucosidase from Aspergillus niger on maltoheptaose and [U-(13)C]maltose.

Oligosaccharides synthesized from a mixture of maltoheptaose and [U-(13)C]maltose with transglucosidase [EC] from Aspergillus niger were investigated. When the reaction mixture was incubated at 15 degrees C for 1h, several types of oligosaccharides with DP (degree of polymerization) 2 to DP8 containing alpha-D-Glcp-(1-->6)-maltoheptaose were detected by liquid chromatography-mass spectrometry (LC-MS) and methylation analysis. Most of these compounds consisted of alpha-(1-->4) linkages in the main chain and alpha-(1-->6) linkages at the non-reducing ends. However, when the reaction mixture was incubated for 96h, most of these products were converted into oligosaccharides with DP2 to DP5 consisting of only alpha-(1-->6) linkages. These results suggested that A. niger transglucosidase rapidly transferred glucosyl residues to maltooligosaccharides, and gradually hydrolyzed both alpha-(1-->4) linkages and alpha-(1-->6) linkages at the non-reducing end, and transformed these into smaller molecules of mainly alpha-(1-->6) linkages.

Carbohydr Res. 2009 Mar 10;344(4):460-5

A novel strategy in production of oligosaccharides in digestive tract: prevention of postprandial hyperglycemia and hyperinsulinemia.

The aim of this study was to evaluate the effects of oral administration of transglucosidase (TG) on postprandial glucose concentrations in healthy subjects. A randomized placebo-controlled three-way crossover trial was separated by a washout period of more than 3 days. Twenty-one normal healthy volunteers, aged 30-61 years old (17 males and 4 females) were selected for this study. The subjects’ health was assessed as normal by prestudy screening. All subjects received 3 types of test meals (3 rice balls: protein, 14.4 g; fat, 2.1 g; and carbohydrate, 111 g: total energy, 522 kcal) with 200 ml water in which 0 mg, 150 mg, or 300 mg of TG was dissolved. Blood samples for estimating plasma glucose and insulin concentrations were collected before and every 30 min after the experiment. As compared to no TG treatment, TG administration tended to prevent a postprandial increase in plasma glucose (p = 0.069: 150 mg of TG vs control) but there were no significant difference among three groups. With regard to the 17 subjects who were suggested to have impaired glucose tolerance, TG significantly decreased the postprandial blood glucose (p<0.05: 150 mg and 300 mg of TG vs control) and marginally decreased insulin concentrations (p = 0.099: 300 mg of TG vs control). These results suggest that TG may be useful for preventing the progression of type 2 diabetes mellitus.

J Clin Biochem Nutr. 2007 Nov;41(3):191-6

An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods.

The aim of this study was to systematically compare postprandial insulin responses to isoenergetic 1000-kJ (240-kcal) portions of several common foods. Correlations with nutrient content were determined. Thirty-eight foods separated into six food categories (fruit, bakery products, snacks, carbohydrate-rich foods, protein-rich foods, and breakfast cereals) were fed to groups of 11-13 healthy subjects. Finger-prick blood samples were obtained every 15 min over 120 min. An insulin score was calculated from the area under the insulin response curve for each food with use of white bread as the reference food (score = 100%). Significant differences in insulin score were found both within and among the food categories and also among foods containing a similar amount of carbohydrate. Overall, glucose and insulin scores were highly correlated (r = 0.70, P < 0.001, n = 38). However, protein-rich foods and bakery products (rich in fat and refined carbohydrate) elicited insulin responses that were disproportionately higher than their glycemic responses. Total carbohydrate (r = 0.39, P < 0.05, n = 36) and sugar (r = 0.36, P < 0.05, n = 36) contents were positively related to the mean insulin scores, whereas fat (r = -0.27, NS, n = 36) and protein (r = -0.24, NS, n = 38) contents were negatively related. Consideration of insulin scores may be relevant to the dietary management and pathogenesis of non-insulin-dependent diabetes mellitus and hyperlipidemia and may help increase the accuracy of estimating preprandial insulin requirements.

Am J Clin Nutr. 1997 Nov;66(5):1264-76

Prebiotics to Fight Diseases: Reality or Fiction?

Bacteria living in the gastrointestinal tract are crucial for human health and disease occurrence. Increasing the beneficial intestinal microflora by consumption of prebiotics, which are ‘functional foods’, could be an elegant way to limit the number and incidence of disorders and to recover from dysbiosis or antibiotic treatments. This review focuses on the short-chain low-digestible carbohydrates (LDCs) which are metabolized by gut microbiota serving as energy source, immune system enhancers or facilitators of mineral uptake. Intake of foods containing LDCs can improve the state of health and may prevent diseases as for example certain forms of cancer. Given the large number of different molecules belonging to LDCs, we focused our attention on fructans (inulin, fructo-oligosaccharides), galacto-oligosaccharides and resistant starches and their therapeutic and protective applications. Evidence is accumulating that LDCs can inhibit bacterial and viral infections by modulating host defense responses and by changing the interactions between pathogenic and beneficial bacteria. Animal studies and studies on small groups of human subjects suggest that LDCs might help to counteract colorectal cancer, diabetes and metabolic syndrome. The action mechanisms of LDCs in the human body might be broader than originally thought, perhaps also including reactive oxygen species scavenging and signaling events.

Phytother Res. 2012 Dec 27

Management of metabolic syndrome through probiotic and prebiotic interventions.

Metabolic syndrome is a complex disorder caused by a cluster of interrelated factors that increases the risk of cardiovascular diseases and type 2 diabetes. Obesity is the main precursor for metabolic syndrome that can be targeted in developing various therapies. With this view, several physical, psychological, pharmaceutical and dietary therapies have been proposed for the management of obesity. However, dietary strategies found more appropriate without any adverse health effects. Application of probiotics and prebiotics as biotherapeutics is the new emerging area in developing dietary strategies and many people are interested in learning the facts behind these health claims. Recent studies established the role of probiotics and prebiotics in weight management with possible mechanisms of improved microbial balance, decreased food intake, decreased abdominal adiposity and increased mucosal integrity with decreased inflammatory tone. Hence, the above “Pharmaco-nutritional” approach has been selected and extensively reviewed to gain thorough knowledge on putative mechanisms of probiotic and prebiotic action in order to develop dietary strategies for the management of metabolic syndrome.

Indian J Endocrinol Metab. 2012 Jan;16(1):20-7

Probiotics, prebiotics, energy balance, and obesity: mechanistic insights and therapeutic implications.

Obesity-related disorders derive from a combination of genetic susceptibility and environmental factors. Recent evidence supports the role of gut microbiota in the pathogenesis of obesity, type 2 diabetes mellitus, and insulin resistance by increasing energy harvest from diet and by inducing chronic, low-grade inflammation. Several studies describe characteristic differences between composition and activity of gut microbiota of lean individuals and those with obesity. Despite this evidence, some pathophysiological mechanisms remain to be clarified. This article discusses mechanisms connecting gut microbiota to obesity and fat storage and the potential therapeutic role of probiotics and prebiotics

Gastroenterol Clin North Am. 2012 Dec;41(4):843-54

High dietary glycemic index and low fiber content are associated with metabolic syndrome in patients with type 2 diabetes.

OBJECTIVE: To investigate possible associations of dietary glycemic index (GI) and fiber content with metabolic syndrome (MetS) in patients with type 2 diabetes. METHODS: In this cross-sectional study, 175 outpatients with type 2 diabetes (aged 61.1 ± 9.7 years; HbA(1c) 7.3% ± 1.4%; diabetes duration of 11 years [range, 5-17]) had food intake assessed by 3-day weighed-diet records. Dietary GI (according to FAO/WHO) and fiber content were categorized as high or low based on median values. MetS was defined according to the 2009 Joint Interim Statement. RESULTS: Patients with MetS (n = 109) had higher 24-hour GI (60.0% ± 6.3% vs 57.5% ± 6.4%), higher breakfast GI (59.8% ± 8.0% vs 55.0% ± 9.9%), and lower fiber intake at 24 hours (17.0 ± 6.6 g vs 21.2 ± 8.0 g), breakfast (1.9 [1.2-3.2] vs 3.1 [1.8-4.9] g), lunch (6.2 [3.9-8.0] vs 7.5 [4.7-9.4] g), and dinner (3.3 [2.1-5.2] vs 4.9 [3.1-6.4] g; p < 0.05 for all comparisons) than patients without MetS. In multivariate analyses, high GI (~60%) of 24 hours (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.10-4.11; p = 0.025), breakfast (OR, 2.20; 95% CI, 1.15-4.21; p = 0.017), and lunch (OR, 2.46; 95% CI, 1.28-4.74; p = 0.007) was associated with MetS. Breakfast (OR, 2.14; 95% CI, 1.04-4.41; p = 0.039) and dinner (OR, 2.27; 95% CI, 1.15-4.49; p = 0.019) with low fiber content were also associated with MetS. When high GI and low fiber intake were combined into the same variable, associations with MetS were maintained. CONCLUSIONS: Increased dietary GI and reduced fiber content were positively associated with MetS, mainly due to breakfast intake, in patients with type 2 diabetes.

J Am Coll Nutr. 2011 Apr;30(2):141-8