Having diabetes is like aging 15 years
Gillian L. Booth and colleagues at the University of Toronto and the Institute for Clinical Evaluative Sciences analyzed the majority of the adult population of Ontario for the current study. They recorded cardiovascular events between April of 1994 and March of 2000 for 379,003 individuals over the age of 20 with diabetes and 9,018,082 without the disease to calculate the age at which a high risk of cardiovascular disease (CVD) developed. The team found that diabetics transitioned into the high risk category 15 years earlier than nondiabetics. Heart attack, stroke, or death from any cause took place at an average of age 41 for diabetic men and at 48 for women with the disease, compared to an average age of 48 and 54 years for nondiabetic men and women.
Death rates within the five age groups analyzed were 2 to 4 times higher in diabetics compared to men and women who did not have diabetes. Although young diabetic adults had coronary heart disease rates that were 12 to 40 times higher than those of nondiabetics, the rates were low enough to avoid being considered high risk.
"Middle-aged and older people with diabetes seem on average to be at high risk of CVD, thus aggressive risk-reduction strategies are warranted for them," Dr Booth stated. "Appropriate thresholds for younger people with diabetes are less clear. At least in the short term, many individuals with diabetes who are younger than 40 years seem to have a low to moderate absolute risk of CVD. Age should be taken into account in targeting of risk reduction in people with diabetes."
Meta-analysis concludes vitamin K supplements reduce bone-loss
A review published in the June 26, 2006 issue of the American Medical Association journal Archives of Internal Medicine concluded that supplementing with either of the commonly available forms of vitamin K is associated with a reduction in bone loss. Vitamin K is synthesized by plants and bacteria, and is available in supplements in the synthetic forms of phytonadione (vitamin K1) or menaquinone-4 (vitamin K2).
The authors, from the University Of York, the University of Surrey, and St Thomas Hospital in London, England analyzed 13 clinical trials involving oral phytonadione and menaquinone supplementation which provided data on bone loss. Seven of the trials, conducted in Japan using menaquinone, also included fracture data.
The researchers found that all of the trials except one demonstrated a benefit for phytonadione and menaquinone in reducing bone loss as determined by bone mineral density. A separate analysis of the seven trials that included the vitamin's effect on fractures demonstrated that menaquinone supplementation was associated with a 60 percent reduction in vertebral fracture risk, a 77 percent reduction in hip fracture risk and an 81 percent reduction in all nonvertebral fracture risk compared to participants who did not receive the vitamin.
In their discussion, the authors observe that there are at least three proteins in bone and cartilage that are dependent upon vitamin K: osteocalcin, matrix gamma-carboxyglutamic acid protein, and protein S. In addition, previous research has found that patients with osteoporosis have low vitamin K blood levels. Based on the findings of the current review, the authors suggest that individuals at risk of fracture be encouraged to consume a vitamin K rich diet.
Cherry juice helps prevent muscle damage during exercise
The results of a study published online in the British Journal of Sports Medicine suggest that drinking cherry juice may help protect the muscles from damage that occurs during exercise.
Declan A. J. Connolly of the University of Vermont, along with colleagues Malachy Mc Hugh and Olga Padilla-Zakour assigned 14 men to drink a bottle of a cherry juice blend or a placebo liquid twice per day for eight days. A bottle of juice provided the equivalent of 50 to 60 tart cherries combined with apple juice. On the fourth day of the study, participants were instructed to perform two sets of 20 repetitions of elbow flexion contractions using one arm. The experiment was repeated two weeks later with the other arm, with the group who received a placebo receiving the cherry juice blend this time and the other group receiving the placebo. Participants rated muscle tenderness, motion, and strength on each day of the study.
Muscle strength among subjects who received cherry juice fell by only 4 percentage points after exercising, compared to 22 points among those who received the placebo. Participants who received cherry juice reported improvement in muscle strength 96 hours after exercising, and less pain. The highest pain scores in the cherry juice drinkers occurred 24 hours following exercise, while among those who received the placebo pain increased for 48 hours.
"The anti-inflammatory properties of cherry juice have been examined before, but the focus of this research was on a new area – muscle damage repair," Dr Connolly commented. "Only two species of mammals suffer this type of muscle damage – horses and humans."
"Current anecdotal evidence suggests the drink may be effective in treatment of arthritis and gout, and thus offer a potentially safer alternative than prescription drugs," he observed.
Silibinin may help prevent or slow lung cancer development
The June 21, 2006 issue of the Journal of the National Cancer Institute reported the finding of Rajesh Agarwal, PhD and his colleagues at the University of Colorado Health Sciences Center in Denver that the compound silibinin, derived from milk thistle, helps prevent the growth and development of lung tumors in mice.
Dr Agarwal's team injected 75 mice with urethane to induce lung tumors, and injected a control group with saline. The animals injected with urethane were provided with normal diets for two weeks, after which they were given diets containing 0.033 percent, 0.1 percent, 0.33 percent, 1 percent, or no silibinin. Ten mice from each group were examined 20 weeks following injection, when lung tumors in this model are in their early stage, while the remainder were examined after 29 weeks.
It was found that mice injected with urethane who received any of the silibinin-containing diets had fewer and smaller tumors than those who received unsupplemented diets at both stages of examination. At 20 weeks, the mean number of larger tumors was reduced by 93 percent among those who received 1 percent silibinin compared to injected mice given the control diet. A significant reduction in tumor size was also observed among the mice examined after 29 weeks, with a 50-83 percent reduction compared to untreated mice. Additionally, silibinin was associated with a reduction in tumor microvessel density of 89 percent compared to the tumors of mice who did not receive the compound, indicating an inhibitory effect on angiogenesis.
"Although the mechanisms by which silibinin interferes with lung tumor growth in preclinical models remains to be explored," the authors note, "these results raise the possibility that silibinin may have chemopreventive activity against lung tumor growth and progression in humans."
Methionine restriction = calorie restriction?
The result of research reported in the June, 2006 issue of the FASEB journal revealed that restricting the diet of just one amino acid, in this case, methionine, provided some of the benefits of calorie restriction found among laboratory animals.
Research in rodents has demonstrated that restricting protein, or one of the amino acids that are the building blocks of protein such as tryptophan or methionine, is associated with an increase in longevity. Scientists at the University of Madrid and University of Lleida in Spain hypothesized that this extension of lifespan could be due to a reduction in mitochondrial reactive oxygen species (ROS) generation and oxidative stress, a phenomenon that has been observed during calorie restriction, which is also known to increase lifespan.
In the current study, one group of rats was allowed to eat as much as they wanted of a diet that contained 0.86 percent L-methionine. A second group received the same amount of food each day that the first group consumed the previous day, except the amount of methionine was restricted to 0.17 percent, and L-glutamic acid was increased from 2.7 percent to 3.39 percent for six to seven weeks.
Mitochondria isolated from the heart and liver were examined at the end of the study. It was found that reactive oxygen species production, oxidative damage to DNA, and protein oxidation were all lower in the mitochondria of mice who received the methionine restricted diet compared to the unrestricted group. The changes observed were similar to those revealed in studies of calorie and protein restriction. "This suggests that the decrease in methionine ingestion can be the single molecular component responsible for the decrease in mitochondrial ROS generation and oxidative stress that occurs during calorie restriction, and thus for part of the decrease in aging rate elicited by this dietary manipulation," the authors conclude.
Common vegetables reduce atherosclerosis in mice
The results of a study published in the July, 2006 issue of the Journal of Nutrition demonstrated that a diet containing five commonly consumed vegetables was associated with decreased atherosclerosis in animals bred to develop the condition. Atherosclerosis describes the formation of plaque on blood vessel walls that can reduce or block blood flow to affected areas.
In research conducted at Wake Forest University School of Medicine by Michael Adams, DVM and his team, mice bred to rapidly develop atherosclerosis due to elevated low-density lipoprotein (LDL) levels were administered diets in which 30 percent of the calorie content was derived from freeze-dried broccoli, carrots, corn, green beans and peas, which are among the top ten vegetables consumed in the U.S. A second group of mice were provided with diets that were vegetable-free.
After 16 weeks, the researchers measured levels of free and ester cholesterol, which accumulate as plaques develop and are used to estimate the extent of plaque deposits. They found that the mice who received vegetables in their diet had 38 percent less plaque than the control group, and had lower cholesterol levels and weights. They also had a 37 percent lower level of a marker of inflammation than the mice that received diets lacking vegetables.
"While everyone knows that eating more vegetables is supposed to be good for you, no one had shown before that it can actually inhibit the development of atherosclerosis," Dr Adams stated. "This suggests how a diet high in vegetables may help prevent heart attacks and strokes."
"It is well known that atherosclerosis progression is intimately linked with inflammation in the arteries," he added. "Our results, combined with other studies, support the idea that increased vegetable consumption inhibits atherosclerosis progression through antioxidant and anti-inflammatory pathways."
Intestinal surgery ups vitamin A deficiency
A report published ahead of print on June 14, 2006 in the British Journal of Ophthalmology concluded that having major intestinal surgery, including intestinal bypass, inflammatory bowel disease surgery, and gallbladder removal, can increase the risk of vitamin A deficiency, even when the surgery was performed as much as 36 years earlier.
T. Chae and R. Foroozan of the Cullen Eye Institute at Baylor College of Medicine in Houston, Texas presented three case reports of patients diagnosed with vitamin A deficiency over a one year period. One patient with night blindness had intestinal bypass surgery 20 years earlier, the second patient, who had decreased vision in one eye, had a partial small and large bowel resection for Crohn's disease 36 years earlier, and the third, a woman with decreased vision in both eyes, had her gallbladder removed 20 years earlier. None of the patients had a history of eye diseases.
Blood testing for retinol, retinyl palmitate, and retinol binding protein levels confirmed vitamin A deficiency, despite the patients having taken vitamin supplements. Intramuscular injection of vitamin A consented to by two of the patients improved visual symptoms within days.
Vitamin A deficiency, while rare in the United States, has been increasingly diagnosed with the popularity of gastric banding and gastric bypass surgery which causes malabsorption of nutrients. The vitamin is used by the rods and cones of the eye, and on the eye surface, where it is needed for the synthesis of epithelial cell RNA and glycoproteins. A number of visual problems, including conjunctival and corneal xerosis, retinopathy, visual loss, and night blindness can result from insufficient levels of vitamin A. "Even a remote history of intestinal bypass surgery . . . should raise the suspicion of vitamin A deficiency," the authors conclude.
Inositol compounds prevent Alzheimer's disease in mouse model
A report published online in the journal Nature Medicine on June 11, 2006 revealed that a type of sugar known as cyclohexanehexol or inositol prevents the accumulation of amyloid beta deposits in the brains of mice bred to develop them. Amyloid beta deposits aggregate into plaques in the brains of humans with Alzheimer's disease, causing inflammation and the death of neurons.
Researchers led by Peter St George-Hyslop at Toronto Western Hospital Research Institute gave epi-inositol or scyllo-inositol to mice with human genes that predispose them to Alzheimer's-type disease as well as to normal mice. Some of the animals received the compounds before the onset of the disease at six weeks of age and continued to receive them until 4 or 6 months of age. Other mice received one of the two compounds at the age of 5 months, when the disease was well established. Control groups of both strains received neither compound.
Administration of either compound to the transgenic mice at 5 weeks resulted in improved cognitive function compared to the untreated transgenic mice at 4 and 6 months. Additionally, mice who received the inositol compounds experienced a reduction in brain amyloid beta levels and pathology, less synaptic loss and inflammation, and lowered mortality. Scyllo-inositol was responsible for a larger and more sustained effect than epi-inositol, and worked when given before as well as after disease onset.
Dr St George-Hsylop noted that the forms of inositol used in the study were not the same as myo-inositol, which is available as a nutritional supplement.
“Alzheimer's disease is probably going to be treated by a cocktail of drugs,” he concluded. “Some of them might be this compound, or one like it, that blocks the toxicity and aggregation of amyloid.”
Sulforaphane helps block metastasis
A report published in the May 22, 2006 issue of the journal Life Sciences revealed the findings of P. Thejass and Girija Kuttan at the Amala Cancer Research Center in Kerala, India that sulforaphane significantly prevented the metastasis of melanoma cells in mice. Sulforaphane is an isothiocyanate found in broccoli and other cruciferous vegetables that has been shown to help protect against chemically-induced tumors.
The current study utilized mice in whom melanoma tumor cells were injected. Five hundred micrograms per kilogram body weight sulforaphane was administered to one group of mice at the same time as the tumor cells were injected, while two other groups received the compound 10 days prior to and 10 days after the cells were injected. A control group of animals injected with tumor cells received no sulforaphane.
The control mice were found to have a significant amount of lung tumors compared to animals who received sulforaphane. Sulforaphane given simultaneously with the tumor cells was the most effective mode of administration, being associated with an inhibition of 95.5 percent of metastases, and an increase in lifespan of 94 percent compared to the control group. Preventive administration was the second most effective mode, which inhibited metastases by 90.51 percent and increased the lifespan of this group by 62.17. Giving sulforaphane after the tumors had developed increased lifespan by 37.85 compared to animals who did not receive the compound. In addition, sulforaphane was associated with a reduction in levels of lung tumor-associated compounds, such as lung hydroxyproline.
In-vitro research showed that sulforaphane inhibited the activation of matrix metalloproteinases, which are enzymes that degrade the cell membrane and facilitate the metastasis of tumors. The authors suggest that sulforaphane's antimetastatic activity may be mainly due to this action.
Cancer-aging link found
A report published in the June 2, 2006 issue of Science revealed the discovery that checkpoint proteins, which prevent the division of defective cells that can lead to cancer, are also involved in limiting life span. The finding reveals an important link between cancer and the increased risk of the disease that occurs with aging.
A research team led by Professor Gordon Lithgow, who started the project at the University of Manchester and completed it at the Buck Institute in California, genetically programmed the roundworm C. elegans to lack checkpoint proteins, which resulted in a 15 to 30 percent increase in the animal's life span.
"We have discovered that proteins that prevent cancer in humans by ensuring that cells don't divide if they are damaged also determine lifespan in the nematode worm," Dr Lithgow stated. "Our research has shown that these 'checkpoint proteins' – thought only to operate in cells that divide – function in cells that no longer divide as well. The fact that they appear to have dual functions opens a new way to study the connection between aging and cancer. If we look at checkpoint proteins as a gear, we have known for a long time that they drive the cancer engine; now we know that they also drive the longevity engine. This discovery has exciting potential as an area of inquiry into potential cellular links between aging and cancer."
Dr Dale Bredesen, who is the Buck Institute's Scientific Director, added, "If we're smart about it, we might be able to design strategies where you could keep checkpoint proteins active in dividing cells and stop them working in cells that no longer divide, such as brain cells. Increasing the survival of brain cells or 'neurons' could provide a new avenue of treatment for neurodegenerative diseases like Alzheimer's."
The Asian paradox
A review by Yale University researchers published in the May, 2006 issue of the Journal of the American College of Surgeons concluded that green tea consumption may be the explanation of the "Asian paradox." Similar to the French paradox, which refers to the hypothesis that red wine protects the French from the adverse cardiovascular effects of a fatty diet, green tea may protect Asians from the adverse effects of smoking. Many people in Asia are smokers, yet there is a lower incidence of cardiovascular disease and cancer than in many countries in which fewer people smoke.
Professor and Chief of Vascular Surgery at Yale's Department of Surgery Bauer Sumpio, MD, and colleagues reviewed over 100 experimental and clinical studies concerning green tea to arrive at their conclusion. He noted that the average 1.2 liters of green tea consumed each day by many Asians provides the antioxidant epigallocatechin gallate (EGCG), which may reduce low density lipoprotein (LDL) oxidation, lower platelet aggregation, regulate lipids, and promote proliferation and migration of smooth muscle cells, which are all factors involved in reducing cardiovascular disease. The compound has also been demonstrated to prevent the growth of some tumors.
Dr Sumpio stated, "We do not yet have a full explanation for the 'Asian paradox,' which refers to the very low incidence of both heart disease and cancer in Asia, even though consumption of cigarettes is greater than in most other countries. But we now have some theories."
Vitamin D reduces blood clots in advanced prostate cancer patients
At the annual meeting of the American Society of Clinical Oncology held in Atlanta, Georgia, Peter Venner, MD of the Alberta Cancer Board's Cross Cancer Institute reported on June 2, 2006 that prostate cancer patients who received the active form of vitamin D experienced a reduction in thrombosis (blood clot formation). Thrombosis affects between 15 to 20 percent of cancer patients, and can become a life-threatening complication.
The discovery was a chance finding in a randomized trial of 250 advanced prostate cancer patients who received the chemotherapy drug Docetaxel along with a placebo or high-dose calcitriol, the active form of vitamin D in the body. The study sought to determine the effect of calcitriol on prostate specific antigen (PSA), a marker of prostate cancer progression, as well as its effect on chemotherapy side effects and survival. The researchers found that men who received calcitriol had fewer chemotherapy side effects, improved survival, and a reduction in venous and arterial thromboses.
While the clinical trial found results for prostate cancer patients, other studies suggest that calcitriol may be safe to use in other cancers. "This is a serendipitous outcome," Dr Venner stated. "It wasn't what we were looking for, but it offers an avenue of investigation that could result in a new class of anticoagulants, which could, in turn, significantly improve outcomes for cancer patients."
A recently activated phase III clinical trial will confirm calcitriol's antithrombotic effect.
Free radical mechanism found
Scientists at Harvard Medical School have found a mechanism behind the damage that oxidative stress causes to cells which results in the deterioration associated with aging and disease. Oxidative stress is caused by highly reactive molecules known as free radicals formed as a byproduct of metabolism. Although free radicals are quenched by antioxidants, the increase in free radical production that occurs with age overwhelms the body's antioxidant defenses, resulting in damage to the cells' DNA, proteins and lipids. The findings were published in the June 1, 2006 issue of the journal Cell.