Health for life

A University of Colorado Cancer Center study published online ahead of print in the journal Nutrition and Cancer describes the laboratory synthesis of the most active component of grape seed extract, B2G2, and shows this synthesized compound induces the cell death known as apoptosis in prostate cancer cells while leaving healthy cells unharmed.

“We’ve shown similar anti-cancer activity in the past with grape seed extract (GSE), but now we know B2G2 is its most biologically active ingredient which can be synthesized in quantities that will allow us to study the detailed death mechanism in cancer cells,” says Alpna Tyagi, PhD, of the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. Tyagi works in the lab of CU Cancer Center investigator and Skaggs School of Pharmacy faculty member, Chapla Agarwal, PhD.

The group has spent more than a decade demonstrating the anti-cancer activity of GSE in controlled, laboratory conditions. For example, previous studies have shown the GSE effectiveness against cancer cells and have also shown its mechanism of action. “But until recently, we didn’t know which constituent of GSE created this effect. This naturally occurring compound, GSE, is a complex mixture of polyphenols and also so far it has been unclear about the biologically active constituents of GSE against cancer cells,” Tyagi says.

Eventually the group pinpointed B2G2 as the most active compound, but, “it’s expensive and it takes a long time to isolate B2G2 from grape seed extract,” Tyagi says.

This expense related to the isolation of B2G2 has limited the group’s further exploration. So instead of purifying B2G2 from GSE, the group decided to synthesize it in the lab. The current study reports the success of this effort, including the ability to synthesize gram-quantity of B2G2 reasonably quickly and inexpensively.

In the paper’s second half, the group shows anti-cancer activity of synthesized B2G2 similar in mechanism and degree to overall GSE effectiveness.

“Our goal all along has been a clinical trial of the biologically active compounds from GSE against human cancer. But it’s difficult to earn FDA approval for a trial in which we don’t know the mechanisms and possible effects of all active components. Theore, isolating and synthesizing B2G2 is an important step because now we have the ability to conduct more experiments with the pure compound. Ongoing work in the lab further increases our understanding of B2G2′s mechanism of action that will help for the preclinical and clinical studies in the future,” Tyagi says.

Research details published in the Molecular Nutrition and Food Research journal explains the potent mechanism exhibited by cruciferous vegetables such as broccoli and cauliflower to ameliorate developing cancer cells. The active photochemical known as sulforaphane targets prostate and other hormone dependent cancer lines and leaves normal healthy cells unaffected.

Vitamin D is vital for making our muscles work efficiently and boosting energy levels, new research from Newcastle University has shown.

A study led by Dr Akash Sinha has shown that muscle function improves with Vitamin D supplements which are thought to enhance the activity of the mitochondria, the batteries of the cell.

A hormone normally produced in the skin using energy from sunlight, Vitamin D can also be found in a few foods – including fish, fish liver oils, egg yolks and fortified cereals but it can also be effectively boosted with Vitamin D supplements.

It is thought around 60% of people in the UK are vitamin D deficient, with children under five, people with dark skin and the elderly being particularly vulnerable. While it has a well-established association with helping in bone formation and a deficiency can lead to rickets, its role in other health issues is just emerging.

The researchers used non-invasive magnetic resonance scans to measure the response to exercise in 12 patients with severe deficiency before and after treatment with vitamin D.

Lead author Dr Akash Sinha who also works within the Newcastle upon Tyne Hospitals NHS Foundation Trust said: "The scans provided a unique window into what is really going on in the muscle as it works.

"Examining this small group of patients with vitamin D deficiency who experienced symptoms of muscle fatigue, we found that those with very low vitamin D levels improved their muscle efficiency significantly when their vitamin D levels were improved."

Alongside poor bone health, muscle fatigue is a common symptom in vitamin D deficient patients. This fatigue could be due to reduced efficiency of the mitochondria: the power stations within each cell of the body.

Mitochondria use glucose and oxygen to make energy in a form that can be used to run the cell - an energy-rich molecule called ATP. Muscle cells need large amounts of ATP for movement and they use phosphocreatine as a ready and available energy source to make ATP. The mitochondria also replenish this phosphocreatine store after muscle contraction and measuring the time taken to replenish these stores is a measure of mitochondrial efficiency: better mitochondrial function is associated with shorter phosphocreatine recovery times.

The team found that these recovery rates significantly improved after the patients took a fixed dose of oral vitamin D for 10-12 weeks. The average phosphocreatine recovery half time decreased from 34.4 sec to 27.8 sec. All patients reported an improvement in symptoms of fatigue after having taken the supplements. In a parallel study, the group demonstrated that low Vitamin D levels were associated with reduced mitochondrial function.

Dr Sinha added: "We have proved for the first time a link between vitamin D and mitochondria function.

"Of the patients I see, around 60% are vitamin D deficient and most people living north of Manchester will struggle to process enough vitamin D from sunlight alone, particularly during winter and spring. So a simple vitamin D tablet could help boost your energy levels – from within the cells."

According to researchers from Washington University in St. Louis, fat cells - at least those in mice - release a protein, called Nampt, that helps the beta cells of the pancreas secrete insulin.

"In the face of increasing insulin resistance," says lead author Shin-ichiro Imai, "this process could be critical for compensating pancreatic beta cell function."

So why do people who are overweight have difficulty metabolizing glucose? Dr. Imai says,

"It may be that in some obese individuals a threshold has been reached so that this mechanism no longer provides adequate compensation. But there may be ways to overcome this threshold."

Those ways involve a compound produced by Nampt, called NMN. NMN circulates in the bloodstream. When it reaches the pancreas in high enough amounts, it stimulates insulin secretion. Mice that were short on Nampt had impaired glucose metabolism, a condition that improved when they were given NMN.

This discovery could lead to new ways of treating insulin resistance and diabetes.
________
The study was reported in the November 7 issue of Cell Metabolism:
Nampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme

Washington University news brief:
Fat Cells Send Message That Aids Insulin Secretion

Photo of four fat cells, from immaturity to full maturity, via University of Medicine and Dentistry of New Jersey: UMDNJ Magazine

One of my earlier posts (Think Twice Before Feeding Your Child Cows Milk) discussed the possibility that early ingestion of cows milk can increase the risk for type 1 diabetes.

Last month, an article in a journal of the American Chemical Society reviewed the literature for this association:

Relation of Time of Introduction of Cow Milk Protein to an Infant and Risk of Type-1 Diabetes Mellitus, Journal of Proteome Research, April, 2008

Its author, Marcia Goldfarb, described a set of conditions which could explain how pancreatic beta cells are destroyed - leading to type 1 diabetes - when cows milk products are fed to infants:

"The newborn intestine does not have complete "closure" and can pass food antigens. Beta Lactoglobulin could generate antibody to glycodelin undermining T cell regulation of beta cells."

Mechanism

1. Beta-lactoglobulin is a protein present in cows milk, but not human milk. "It has the largest concentration of any whey protein in bovine milk. (Goldfarb)" Glycodelin is a human protein that affects our immune system, regulating our T-cells.
   
   
2. The cow beta-lactoglobulin and the human glycodelin have similar structures, such that an infants body may generate antibodies not just for the foreign beta-lactoglobulin, but also for the endogenous glycodelin.
   
   
3. Type 1 diabetes is thought to be caused by autoimmune destruction of pancreatic beta cells by T-cells. Destruction of glycodelin (by the antibodies generated to destroy the foreign cows milk protein) may allow proliferation of these beta-cell-destroying T-cells.

In a small investigation, Goldfarb indeed found antibodies to beta-lactoglobulin in the serum of children with type 1 diabetes. Those she tested who did not have diabetes did not have these antibodies.
________