Arthritis patients have surgical options other than knee replacement

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

Washington D.C., May 20: While a dairy-rich diet is helpful in meeting the body's calcium requirement, outcomes of a large international study links eating at least two daily servings of dairy with lower risks of diabetes and high blood pressure.

The dairy-rich diet also proved to lower the cluster of factors that heighten cardiovascular disease risk (metabolic syndrome). The study was published online in journal BMJ Open Diabetes Research & Care.

The observed associations were strongest for full-fat dairy products, the findings indicated.

Previously published research has suggested that higher dairy intake is associated with a lower risk of diabetes, high blood pressure, and metabolic syndrome. But these studies have tended to focus on North America and Europe to the exclusion of other regions of the world.

To see whether these associations might also be found in a broader range of countries, the researchers drew on people taking part in the Prospective Urban Rural Epidemiology (PURE) study.

Participants were all aged between 35 and 70 and came from 21 countries: Argentina; Bangladesh; Brazil; Canada; Chile; China; Colombia; India; Iran; Malaysia; Palestine; Pakistan; Philippines, Poland; South Africa; Saudi Arabia; Sweden; Tanzania; Turkey; United Arab Emirates; and Zimbabwe.

Usual dietary intake over the previous 12 months was assessed by means of Food Frequency Questionnaires. Dairy products included milk, yogurt, yogurt drinks, cheese and dishes prepared with dairy products, and were classified as full or low fat (1-2 percent).

Butter and cream were assessed separately as these are not commonly eaten in some of the countries studied.

Information on personal medical history, use of prescription medicines, educational attainment, smoking and measurements of weight, height, waist circumference, blood pressure and fasting blood glucose were also collected.

Data on all five components of the metabolic syndrome were available for nearly 113,000 people: blood pressure above 130/85 mm Hg; waist circumference above 80 cm; low levels of (beneficial) high-density cholesterol (less than 1-1.3 mmol/l); blood fats (triglycerides) of more than 1.7 mmol/dl; and fasting blood glucose of 5.5 mmol/l or more.

Average daily total dairy consumption was 179 g, with full-fat accounting for around double the amount of low fat: 124.5+ vs 65 g.

Some 46, 667 people had metabolic syndrome--defined as having at least 3 of the 5 components.

Total dairy and full-fat dairy, but not low-fat dairy, was associated with a lower prevalence of most components of metabolic syndrome, with the size of the association greatest in those countries with normally low dairy intakes.

At least 2 servings a day of total dairy were associated with a 24 percent lower risk of metabolic syndrome, rising to 28 percent for full-fat dairy alone, compared with no daily dairy intake.

The health of nearly 190,000 participants was tracked for an average of nine years, during which time 13,640 people developed high blood pressure and 5351 developed diabetes.

At least 2 servings a day of total dairy was associated with a 11-12 percent lower risk of both conditions, rising to a 13-14 percent lower risk for 3 daily servings. The associations were stronger for full fat than they were for low-fat dairy.

This is an observational study, and as such can't establish the cause. Food frequency questionnaires are also subject to recall, and changes in metabolic syndrome weren't measured over time, all of which may have influenced the findings.

Nevertheless, the researchers suggest: "If our findings are confirmed in sufficiently large and long term trials, then increasing dairy consumption may represent a feasible and low-cost approach to reducing [metabolic syndrome], hypertension, diabetes, and ultimately cardiovascular disease events worldwide."

Washington D.C., Jan 25: A new study conducted by a team of researchers reveals why individuals who have a history of early life adversity (ELA) are disproportionately prone to opioid addiction.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers simulated ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

The study found that unpredictable, fragmented early life environments may lead to abnormal maturation of certain brain circuits, which profoundly impacts brain function and persists into adolescence and adulthood.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers implanted ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.