Pleasant Stone Farm Clinical Reports

They say sunshine can cheer you up, but insufficient levels of the sunshine vitamin may also increase your risk of developing depression, says a joint study from Italy and the US.

Both men and women over the age of 65 have increased risk of depressive symptoms is they have low vitamin D levels, with the association stronger in women than men, according to findings published in the Journal of Clinical Endocrinology & Metabolism.

“Understanding the potential causal pathway between vitamin D deficiency and depression requires further research,” wrote the researchers, led by Luigi Ferrucci from the US National Institute on Aging.

And the World Health Organization (WHO) forecasts that within 20 years more people will be affected by depression than any other health problem; it ranks depression as the leading cause of disability worldwide, with around 120 million people affected.

This is not the first time that vitamin D has been linked to symptoms of depression. Dutch scientists reported in 2008 in the Archives of General Psychiatry that low levels of the vitamin and higher blood levels of the parathyroid hormone (PTH) were associated with higher rates of depression among 1,282 community residents aged between 65 and 95.

Furthermore, a review by Bruce Ames and Joyce McCann from the Children’s Hospital and Research Center Oakland highlighted the role of the vitamin in maintaining brain health, noting the wide distribution of vitamin D receptors throughout the brain.

According to the review (FASEB Journal, Vol.22, pp. 982-1001), the vitamin has been reported to affect proteins in the brain known to be directly involved in learning and memory, motor control, and possibly even maternal and social behaviour. Depression in the elderly is highly prevalent and can increase the risk of medical illnesses, worsen the outcome of other medical illnesses, and may increase mortality.

Study details

Ferrucci and his co-workers analysed data from 531 women and 423 men aged over 65 participating in the Italy-based InCHIANTI Study. The participants were followed for six years and their depressive symptoms assessed using the Center for Epidemiological Studies-Depression Scale (CES-D).

Results showed that women with blood levels of 25(OH)D – the storage form of the vitamin in the blood – below 50 nmol/litre had significantly higher scored on the CES-D, than women with vitamin D levels about 50 nmol/litre.

Similar relationships were observed in men, but the association was not as strong, said the researchers.

“Our findings suggest that hypovitaminosis D is a risk factor for the development of depressive symptoms in older persons,” they wrote.

However, the study does not prove causality, and further study is required.

Mood food

The link between diet and mood may extend to a variety of nutrients, according to the literature. Scientists from around the world have reported that ingredients such as zinc, omega-3, folate, St John’s wort, green tea and red clover may reduce the symptoms of depression.

Source: Journal of Clinical Endocrinology & Metabolism
Published online ahead of print, doi:10.1210/jc.2010-0347
“Serum 25-Hydroxyvitamin D and Depressive Symptoms in Older Women and Men”
Authors: Y. Milaneschi, M. Shardell, A.M. Corsi, R. Vazzana, S. Bandinelli, J.M. Guralnik, L. Ferruci

Coffee is one of the most pervasive beverages globally. It speaks the same language, and bears the same love no matter what country you’re in. It has been touted for its many health benefits, and well as frowned upon for its acidic nature and effect on blood pressure. But researchers continue to delve into its potential, never-ending benefits and questionable effects. Italian researchers recently reported caffeinated coffee acutely induced unfavorable cardiovascular effects, especially on endothelial function; and during the fasting state, insulin secretion was reduced after caffeinated coffee ingestion (Eu J Clin Nutr. 2010;64:483–489).

A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double blind, crossover study. Subjects ingested one cup of caffeinated and one cup of decaffeinated Italian espresso coffee in random order at five- to seven-day intervals. Following caffeinated ingestion, brachial artery flow-mediated dilation (FMD) decreased progressively and significantly, but it did not significantly increase after decaffeinated ingestion. Similarly, caffeinated coffee significantly increased both systolic and diastolic blood pressure; this effect was not observed after decaffeinated ingestion. Blood glucose concentrations remained unchanged after ingestion of both caffeinated and decaffeinated, but insulin and C-peptide blood concentrations decreased significantly only after caffeinated ingestion.

Daily supplements of magnesium may improve lung function in asthmatics, and improve their quality of life, says a new study from America.

Measures of lung capacity increased by about 6 per cent during six months of magnesium supplementation, and improvements were also observed in the bronchial response to methacholine, a chemical that produces constriction of the lungs, according to findings published in the Journal of Asthma.

“Although there is conflicting research regarding magnesium supplementation and asthma outcomes, this study adds to the body of research that shows a beneficial response to magnesium supplementation in people who have mild to moderate asthma,” wrote researchers, led by Alexandra Kazaks from Bastyr University in Kenmore, Washington State.

According to the European Federation of Allergy and Airway Diseases Patients Association (EFA), over 30m Europeans suffer from asthma, costing Europe €17.7bn every year. The cost due to lost productivity is estimated to be around €9.8bn.

Epidemiological studies have reported beneficial effects of magnesium on asthma occurrence and management, but less than half of adults in the US consume the recommended levels of the mineral, according to the National Health and Nutrition Examination Survey (NHANES) for 1999-2000.

In order to test the hypothesis that magnesium supplements could improve lung function, Dr Kazaks and her co-workers recruited 55 mild-to-moderate asthmatics aged between 21 and 55 to participate in their randomized placebo-controlled, double-blind trial. The participants were randomly assigned to receive either the a daily dose of 340 milligrams of magnesium or placebo for 6.5 months.

At the end of the study, a 6 per cent improvement in lung function, measured as the peak expiratory flow rate (PEFR), was observed in the magnesium group, and not in the placebo group.

Furthermore, 20 per cent more methacholine was needed in the magnesium group to produce bronchoconstriction to the same degree as seen in the placebo group.

Quality of life, a subjective measure obtained by questionnaire, only improved in the magnesium group, added the researchers.

Commenting on the potential mechanism, Dr Kazaks and her co-workers noted that magnesium may influence the properties of cell membranes, thereby improving offer the ability of the lungs to expand. The mineral may also offer anti-inflammatory properties, which could improve asthma control, they said.

Source: Journal of Asthma
February 2010, Volume 47, Issue 1, Pages 83-92
“Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial”
Authors: A.G. Kazaks, J.Y. Uriu-Adams, T.E. Albertson, S.F. Shenoy, J.S. Stern

Sulforaphane, a compound derived from broccoli and broccoli sprouts, could help prevent or treat breast cancer by inhibiting cancer stem cells (CSCs), found a new US study.

Researchers believe that eliminating the CSCs is key to controlling cancer and in findings published in Clinical Cancer Research they found that, in both mice and cell cultures, sulforaphane targeted and killed the cancer stem cells and prevented new tumours from growing.

Recent studies, report the authors, indicate that CSCs have the capacity to drive tumour resistance and relapse/recurrence of cancer, with evidence building for the theory that a variety of cancers are driven and sustained by a small proportion of CSCs.

According to the American Cancer Society, 94,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease.

The researchers argue that a lack of efficacy of current chemotherapies in advance and metastatic disease requires novel approaches to specifically target CSC populations.

The anticancer efficacy of sulforaphane, derived from broccoli/broccoli sprouts, has been evaluated in various cancers and the risk of premenopausal breast cancer was shown to be inversely associated with broccoli consumption, they added.

Furthermore, as a chemoprevention agent, sulforaphane possesses many advantages, such as high bioavailability and low toxicity. “Sulforaphane from broccoli extracts is efficiently and rapidly absorbed in the human small intestine and distributed throughout the body,” said the authors.

Clinical trials

These previous studies, said the researchers, provide a strong rationale for investigating the chemoprevention property of sulforaphane in clinical trials, and the authors said that its chemoprevention properties against cancer are through both ‘blocking’ and ‘suppressing’ effects.

The concentrations of sulforaphane used in the study were higher than what can be achieved by eating broccoli or broccoli sprouts, said the team, and they added that prior research suggests the concentrations needed to impact cancer can be absorbed by the body from the broccoli extract, but side effects are not known.

While the extract is available in capsule form as a supplement, concentrations are unregulated and will vary, claim the researchers.

And they revealed that they are currently developing a method to extract and preserve sulforaphane and that they will then be developing a clinical trial to test it for the prevention and treatment for breast cancer.

“This research suggests a potential new treatment that could be combined with other compounds to target breast cancer stem cells. Developing treatments that effectively target the cancer stem cell population is essential for improving outcomes,” says lead researcher Dr Max Wicha, distinguished professor of oncology and director of the U-M Comprehensive Cancer Center.

The study

The researchers said that they took mice with breast cancer and injected varying concentrations of sulforaphane from the broccoli extract, using used several established methods to assess the number of cancer stem cells in the tumours.

The authors explained that an Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro, while a nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumour growth upon cell reimplantation in secondary mice.

The potential mechanism was investigated using Western blotting analysis and ?-catenin reporter assay, they added.

The researchers found that sulforaphane (1-5 ?mol/L) decreased aldehyde dehydrogenase–positive cell population by 65 per cent to 80 per cent in human breast cancer cells and reduced the size and number of primary mammospheres by 8- to 125-fold and 45 per cent to 75 per cent, respectively.

Daily injection with 50 mg/kg sulforaphane for two weeks reduced aldehyde dehydrogenase–positive cells by >50 per cent in nonobese diabetic and severe combined immunodeficient xenograft tumours, they found.

And, the researchers added that sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumour growth after the reimplantation of primary tumour cells into the secondary mice, they added.

“Our study identified the down regulation of Wnt/?-catenin self-renewal pathway by sulforaphane as one of the possible mechanisms for its efficacy,” they concluded.

The researchers noted treatment with sulforaphane had little effect on the normal cells.

Source: Clinical Cancer Research
Published online ahead of print: doi: 10.1158/1078-0432.CCR-09-2937
Title: Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells
Authors: Y. Li, T. Zhang, H. Korkaya, S. Liu, H. Fang Lee, B. Newman, Y. Yu, S. G. Clouthier, S. J. Schwartz, M. S. Wicha, D. Sun

High doses of resveratrol may improve blood flow in the brain and potentially boost brain health, say results of a new human study from the UK.

A single dose of 250 or 500 milligrams of resveratrol was found to boost blood flow in the brain but did not affect cognitive performance, according to new findings published in the American Journal of Clinical Nutrition.

“The results of the current study provide the first indication in humans that resveratrol may be able to modulate cerebral blood flow variables,” wrote the researchers, led by David Kennedy from the Brain, Performance and Nutrition Research Centre at Northumbria University.

“Thus, it seems reasonable to suggest that the potential effects of this molecule on brain function deserve a great deal more research attention with a clear focus on both healthy humans and pathologic groups,” they added.

The promise of long life

Resveratrol, a powerful polyphenol and anti-fungal chemical, is often touted as the bioactive compound in grapes and red wine, and has particularly been associated with the so-called ‘French Paradox’. The phrase, coined in 1992 by Dr Serge Renaud from Bordeaux University, describes the low incidence of heart disease and obesity among the French, despite their relatively high-fat diet and levels of wine consumption.

Interest in the compound exploded in 2003 when research from David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells. The research, published in Nature, was greeted with international media fanfare and ignited flames of hope for an anti-ageing pill.

According to Sinclair’s findings, resveratrol could activate a gene called sirtuin1 (Sirt1 – the yeast equivalent was Sir2), which is also activated during calorie restriction in various species, including monkeys.

Since then studies in nematode worms, fruit flies, fish, and mice have linked resveratrol to longer lives. Other studies with only resveratrol have reported anti-cancer effects, anti-inflammatory effects, cardiovascular benefits, anti-diabetes potential, energy endurance enhancement, and protection against Alzheimer’s.

Bill Sardi, co-founder and president of Resveratrol Partners, says that: “Resveratrol has the biological effects of so many drugs wrapped up in one molecule.”.

Study details

The new randomized, double-blind, placebo-controlled, crossover study, which involved 22 healthy adults, now suggests a role for the compound in brain health.

Dr Kennedy and his co-workers randomly assigned the participants to receive placebo, or one of two doses of trans-resveratrol (250 or 500 milligrams, Biotivia Bioceuticals, Austria). Forty-five minutes after the dose, the blood flow and cognitive performance of the participants was measured over a 36 minute period.

Results showed that resveratrol produced a dose-dependent increase in cerebral blood flow, but no increase in the placebo group. The researchers also noted an increase in levels of deoxyhemoglobin after both doses of resveratrol, which they said was indicative of increased oxygen extraction and utilisation.

No effect on cognitive function was noted, however.

“One key issue regarding resveratrol and other polyphenols is that of the low bioavailability of the parent molecule in humans,” wrote the researchers. “The results here confirm that orally administered resveratrol can modulate brain function in humans.

“Whether this is as a consequence of the very low concentrations of the parent molecule seen here in plasma, the action of the much higher concentrations of its glucuronide and sulfate conjugates or other metabolites, or the conversion of these metabolites back to the parent form once they reach target tissues remains to be elucidated,” they added.

Dosage questions

The news has not been welcomed by all. Sardi notes that a high dose as used in this study may produce problems over the long-term. Sardi told NutraIngredients last year that the compound is a chelator of copper. “Copper is found in red blood cells and collagen, amongst other places,” he said. “Resveratrol is not suitable for children or pregnant women. Resveratrol would not be suitable in a food snack bar for children.”

Source: American Journal of Clinical Nutrition
Published online ahead of print, doi:10.3945/ajcn.2009.28641
“Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation”
Authors: D.O. Kennedy, E.L. Wightman, J.L. Reay, G. Lietz, E.J. Okello, A. Wilde, C.F. Haskell

New research has suggested that bisphenol A (BPA) could be responsible for altered hormone levels in men.

The US study by John D Meeker et al measured urinary concentrations of BPA and compared them to levels of serum thyroid and reproductive hormone levels in 167 men from an infertility clinic.

BPA exposure and hormone levels

The paper, published in the journal Environmental Science and Technology, said BPA was detected in 89 per cent of urine samples with a media range of 1.3 ng/mL. It also found that men with higher urine BPA concentrations had higher blood levels of follicle-stimulating hormone (FSH) and lower levels of inhibin B. Raised FSH and depressed inhibin B have been associated with poorer sperm quality in humans.

The study also highlighted a fall in the ratio of estrogen to testosterone. This could reflect an anomaly in the production or elimination of these hormones. Lower thyroid-stimulating hormone (TSH) was also observed when data on multiple BPA measurements were used to assess exposure, suggesting excessive thyroid hormone.

The researchers noted that the number of human studies on the effects of the chemical, used in polycarbonate baby bottles and the epoxy linings of food and beverage cans, are limited.

The research team said that its overall conclusions were supported by findings from other studies on animals that have linked altered hormone levels with BPA exposure.

Study limitations

But the group pointed out that its work had “several limitations” as it said its findings need to be substantiated by further research. The most significant of these was that because levels of BPA and hormones were measured at the same time, there was the possibility that hormonal levels changed the concentration of BPA, rather than the reverse. Exposure measure error and the fact that all the subjects were recruited from an infertility clinic were factors that may also have skewed the results, said the study.

Despite these reservations, the study concluded: “Human exposure to BPA may be associated with alterations in circulating hormone levels.”

The continued safe use of BPA in food packaging is currently being scrutinised by both the US Food and Drug Administration and the European Food Safety Authority (EFSA). Presently, Canada and Denmark are the only two countries to have banned its use in food containers or packaging for children aged 0-3.

Urinary Bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic by Meeker, JD, AM Calafat and R Hauser.

Source: Environmental Science and Technology