Vitamin D linked to colon cancer protection: Meta-analysis

High blood levels of vitamin D are associated with a reduced risk of colorectal cancer, according to a new meta-analysis of observational studies from an international team of researchers.

Analysis of data from nine studies revealed that, for every 10 nanograms per milliliter increase in levels of vitamin D (25-hydroxyvitamin D) the associated risk of colorectal cancer decreased by 15 percent.

On the other hand, no association was observed between vitamin D levels and the risk of breast or prostate cancer, say results published in the International Journal of Cancer.

Shining light on the sunshine vitamin

Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.

D and the big C

The link between vitamin D intake and protection from cancer dates from the 1940s when Frank Apperly demonstrated a link between latitude and deaths from cancer, and suggested that sunlight gave "a relative cancer immunity".

Since then there have been numerous studies suggesting associations between vitamin D and lower risks of certain cancers.

There is growing evidence that 1,25(OH)2D has anticancer effects, but the discovery that non-kidney cells can also hydroxylate 25(OH)D had profound implications, implying that higher 25(OH)D levels could protect against cancer in the local sites.

The new meta-analysis, led by Philippe Autier from the International Prevention Research Institute (IPRI) in Lyon, France, adds to the subject, while also showing the relationship between vitamin D and cancer is ambiguous, depending on the type of cancer.

Indeed, a recent meta-analysis published in the European Journal of Cancer (doi: 10.1016/j.ejca.2010.03.037) concluded that the association between vitamin D and breast cancer is still ambiguous.

New analysis

Dr Autier and his co-workers analyzed data from 35 epidemiological studies of 25(OH)D levels and colorectal, breast and prostate cancer.

The analysis showed that for every 10 nanograms per milliliter increase in 25(OH)D levels the associated risk of colorectal cancer decreased by 15 percent, while the risk of breast cancer was associated with an 11 percent decrease. However, when the researchers restricted their analysis to prospective studies only, the breast cancer risk was decreased by only 3 percent, whereas data from case-control studies indicated a risk reduction of 17 percent.

“A non-significant decreased risk of breast cancer risk was associated with higher serum 25-hydroxyvitamin D, but results from prospective studies only did not support an association between vitamin D status and breast cancer,” said the researchers.

No association between vitamin D levels and prostate cancer were observed at all.

“If additional observational studies of vitamin D and cancer are proposed, they should adopt different designs, such as assessment of serum 25-hydroxyvitamin D colorectal at different points in time, or longer follow-up of subjects,” wrote the researcher.

“To assess whether vitamin D status is a risk factor or a risk marker for colorectal cancer, it is likely that new randomized trials will need to be organized to test whether increasing the 25-hydroxyvitamin D level changes the risk of colorectal cancer, and to determine how much of an increase is required to change the risk of cancer sufficiently to be useful as a public health measure,” they concluded.

Source: International Journal of Cancer
15 March 2011, Volume 128, Issue 6, pages 1414–1424
“Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma”
Authors: S. Gandini, M. Boniol, J. Haukka, G. Byrnes, B. Cox, M.J. Sneyd, P. Mullie, P. Autier



Study highlights vital role of magnesium in type 2 diabetes

Low magnesium status may exacerbate the symptoms of type 2 diabetes by further influencing insulin status, according to new research.

The study, published in Clinical Nutrition, finds that long-term hyperglycemia (a condition that leads to excess levels of magnesium in the urine) in patients with type-2 diabetes increases the risk of chronic complications such as nephropathy and may exacerbate and aggravate other clinical conditions associated with diabetes.

The authors said that an adequate magnesium intake is essential for subjects with type-2 diabetes, noting that magnesium intake was inadequate in most (82 percent) of the diabetic subjects studied.

“The results presented here show that magnesium intake by the study population was inadequate and that a high percentage of individuals presented alterations in the status of this mineral,” said the authors, led by Cristiane Hermes Sales from the Department of Food and Experimental Nutrition at the University of São Paulo, Brazil.

Magnesium

Magnesium is an essential in the regulation of many cellular processes and functions as a cofactor in a wide range of metabolic reactions.

Variations in the distribution of magnesium within the body are associated with several disease states, especially diabetes – a disorder which represents a global public health concern.

Sales and colleagues explained that the function of insulin is dependent on magnesium, as it is responsible for the activation of insulin receptors and for stimulation of proteins and substrates involved in insulin signaling.

Previous research has suggested the magnesium intake of patients with diabetes to often be below recommended levels. The researchers noted that there is also evidence that the magnesium status of patients with diabetes tends to alter, and that low levels may influence the evolution of the disease by generating further complications.

“Although some epidemiological studies have suggested that adequate magnesium intake reduces the risk of development of type 2 diabetes, there are still contradictions with respect to the role of low magnesium intake as a predictor factor for this disease,” said Sales and co workers.

The new research assessed magnesium intake status in patients with type 2 diabetes, in order to identify the parameters that best predict alterations in fasting glucose and plasma magnesium.

Study details

Sales and colleagues reported that 77 percent of participants presented one or more magnesium status parameters below the cut-off points for deficiency.

The glycemic levels of patients with type-2 diabetes were found to be influenced by magnesium levels.

The authors reported that concentrations of plasma magnesium were inversely correlated with fasting and 2-h post meal glucose levels, adding that levels of urine magnesium were directly associated with fasting glucose.

Within subjects evaluated, 63 percent were found to have low concentrations of plasma magnesium – indicating alterations in the compartmentalization of this mineral, according to the authors.

The authors said that since magnesium is essential, owing to its involvement in the magnesium-ATP complex that takes part in all transfer reactions that use and supply energy, it is not surprising that deficiency of the mineral is implicated in the impairment of metabolic control.

They concluded that impaired kidney function may lead to high levels of magnesium in the urine, which together with low magnesium intake can induce a rise of glucose in the blood.

Source: Clinical Nutrition
Published online ahead of print, doi: 10.1016/j.clnu.2010.12.011
“Influence of magnesium status and magnesium intake on the blood glucose control in patients with type 2 diabetes”
Authors: C.H. Sales, L.F.C. Pedrosa, J.G. Lima, T.M.A.M. Lemos, C. Colli

Metabolic typing may bring dawn of personalised nutrition

Personalized nutrition – seen by many as the future of nutrition – may take a step closer as scientists apply the metabolomics approach to identify individual metabolic ‘types’.

A study funded through the European Nutrigenomics Organisation (NuGO) found that it is possible to characterize individual responses to fasting, and to take a ‘snapshot’ of small metabolic changes after 36 hours of fasting.

The study’s findings, published in the journal Metabolomics, identified a number of metabolites and hormones not previously associated with fasting. The researchers, led by Hannelore Daniel from the ZIEL Research Centre for Nutrition and Food Sciences in Germany, also found high variability between individuals for certain markers, including leptin, the satiety hormone.

“This study shows how it is possible to use metabolomics to characterize the different responses of individuals to nutritional or physiological stress,” said Professor Ian Johnson from the Institute of Food Research in the UK.

“By using the same approach applied to a large number of volunteers, we hope in the future to be able to divide the population into metabolic “types”, an important step towards personalized nutrition,” said co-researcher Professor Ian Johnson from the Institute of Food Research in the UK.

The rise of ‘omics’

Many food companies – both ingredient suppliers and food manufacturers are taking the potential of nutrigenomics very seriously. Companies such as Nestle, DSM, and Chr Hansen are all investing heavily in the area. However, actual products are as yet, scarce.

Nutrigenomics is seen by many as the future of nutrition. Nutrigenomics is defined as how food and ingested nutrients influence the genome (personalized nutrition). Nutrigenetics is defined as how a person's genetic make-up affects a response to diet (individual nutrition). The difference between the two is important.

Study details

Ten participants were recruited for the study at the Rowett Institute of Nutrition and Health, University of Aberdeen in Scotland. Following four overnight fast the participants provided blood, saliva and urine samples. The fasting period was extended to 36 hours for the last sampling day.

Results showed that, of the 377 products analyzed, 44 per cent of them were shown to change after prolonged fasting of 36 hours compared with overnight fasting (12 hours). Some of these markers were already known to be ‘fasting markers’ but many metabolites and hormones that were altered associated with fasting for the first time in this study.

“We now have a clear fasting signature,” said Dr Daniel.

The researchers noted a complete change in the body’s fuel management system: Specifically, the researchers noted a significant decrease in leptin, the satiety hormone, but this extent of this varied between individuals. Furthermore, ketone levels increased in the urine, again with inter-individual difference, while blood ketone levels rose by a similar amount in all volunteers, added the researchers: The presence of plasma ketone bodies is indicative of tissue fat being broken down.

“This is the first study to our knowledge that has applied metabolomics to comprehensively assess the response to prolonged fasting in human volunteers,” wrote the researchers.

“In addition to well-known markers that characterize this catabolic state (such as NEFA, glycerol and ketone bodies in plasma) we have identified some 100 new metabolites in blood and urine that change in the fasting state. In this respect we provide a snapshot of the ‘catabolic metabolome’ that may be taken as a mirror image of the ‘anabolic metabolome’ reported in three recent metabolomics studies in human volunteers that used the oral glucose tolerance test (OGTT) as a challenge.”

Source: Metabolomics
Published online ahead of print, doi: 10.1007/s11306-010-0255-2
“Metabolomics of prolonged fasting in humans reveals new catabolic markers”
Authors: I. Rubio-Aliaga, B. de Roos, S.J. Duthie, L.K. Crosley, C. Mayer, G. Horgan, I.J. Colquhoun, G Le Gall, F. Huber, W. Kremer, et al.

Vitamin D supplement use increases 50% among US users; herbs slide, finds survey

Vitamin D penetration has jumped 50% in the past two years in the US, according to a new survey of 6000 supplement buyers conducted by product tester and market scrutineer, ConsumerLab.com, that also recorded dwindling herbal interest.

Its 105-page report found vitamin D use had skyrocketed, especially among women who also were more likely to use calcium and probiotics, and that omega-3 fish oil supplements were exerting a “growing dominance”, used by 75.7 percent of respondents as opposed to 74 percent in 2009.

Unlike many of the other 31 supplement types that featured in the survey, fish oil consumption was ubiquitous among all age groups and both genders.

ConsumerLab.com found 56.2 percent of people surveyed were vitamin D supplement users, compared to 47.9 percent in the 2009 survey and 36.9 percent in 2008 – a 52 percent hike.

“In contrast to fish oil, vitamin D use increased with age and by gender – 61 percent of women used vitamin D compared to 51 percent of men,” ConsumerLab.com president, Tod Cooperman told NutraIngredients-USA.com

Multivitamin consumption rates dropped slightly to 70.1 percent from 72 percent in 2009 among those polled – taken from ConsumerLab’s e-newsletter subscription list.

Botanicals took a hit in 2010 with only 37.6 pecent or respondents reporting using them compared with 44 percent in 2009. Glucosamine/chondroitin fell from 38.5 percent to 35.3 percent.

Online outlets were the most popular with 46.5 percent of people using them, compared to 44.1 percent in 2009 and 39.9 percent in 2008. Vitamin stores, mass merchants and direct distributors registered a small drop in patronage.

Other findings included:

• Men were more likely than women to have taken coQ10, herbs and extracts, glucosamine/chondroitin, vitamin E, resveratrol, amino acids, nutrition drinks and powders.
• Younger adults (35-44) were more likely than older adults (75-84) to have used multivitamins, amino acids, nutrition/protein drinks and powders, green tea, nutrition bars and iron.
• Older adults were more likely to have used vitamin D, calcium, CoQ10, vitamin C, vitamin E, resveratrol, vitamin K, and red yeast rice.

Calcium passed CoQ10 to become the fourth most popular supplement with use rising from 51.2 percent in 2009 to 55.3 percent last year. CoQ10 dropped from 55.3 percent to 51.2 percent over the same period.

Protein Is Found to Boost Memory

The hunt for a substance that can improve memory took a promising turn Wednesday, as researchers said they had found a method that appears to reduce forgetting in rats. WSJ's Shirley Wang reports.

According to a study published in the journal Nature, scientists from Mount Sinai School of Medicine in New York showed for the first time that a molecule that occurs naturally in the human brain during memory formation appeared to help rats enhance the strength and duration of some types of memories.

Researchers said that when the substance--known as IGF-II, a protein-like molecule important for cell growth and development as well as tissue repair--was blocked from the brain, the rats didn't remember what they had learned.

The findings are notable in part because they showed improvement in an area of memory known as declarative memory--the ability to remember places, facts and things. Declarative memory is affected in Alzheimer's disease and other forms of dementia, and researchers have long sought ways to improve or preserve it.

It is too early to say whether IGF-II will be useful in humans, but the substance may hold more promise than molecules that have been studied up to now, according to Elizabeth Phelps, a cognitive neuroscientist at New York University who studies human learning and memory. Dr. Phelps, who wasn't involved in the study, called the Nature research "rigorous" and thoroughly conducted.

One advantage of IGF-II is that it can cross the blood-brain barrier, so it could potentially be administered through the bloodstream or as a vapor through the nose, rather than injected directly into the brain. And because it exists in the body already, it's unlikely to be toxic.

However, researchers will watch for unwanted effects on other cells in the body, said Cristina Alberini, a neuroscience professor at Mount Sinai and the senior author of the paper.

Certain proteins and molecules are needed to build and strengthen connections between nerve cells in the brain to form new long-term memories, and IGF-II appears to be one of those molecules. But more research is needed, according to Dr. Alberini.

"The more we know, the more we're going to uncover what are the steps that make memory strong," she said. "Then we'll get ideas for other [molecular] targets."

In the study, the rats were placed in a two-compartment cage where they would receive a mild foot shock at one end. They quickly learned to avoid that area. Some rats were then given an injection of IGF-II, in a part of their brain called the hippocampus. Even weeks later, rats that had received the IGF-II exhibited greater avoidance of the location than rats that had a control injection of another growth factor or saline solution.

The effect was seen only in certain parts of the brain. IGF-II didn't appear to improve memory in the amygdala, which deals more with memories of emotional reactions like fear.

The next step is to administer IGF-II to the entire body to see if it can produce the same memory-boosting effects as direct injection into brain regions, Dr. Alberini said.