Higher levels of Omega-3 fatty acids derived from seafood linked to healthy aging

Higher serum levels of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) are linked to increased survival without chronic diseases and cognitive and physical dysfunction reports the results of a new study published online October 17 in BMJ.

Fish-oil and long-chain omega-3 fatty acids (EPA, DPA, and DHA) are well known for their role in human well-being. As evident through many previous studies, omega-3 fatty acids are involved in maintaining cardiovascular health, but their role in overall healthy aging is not well established.

This study is unique because unlike previous studies, the researchers from Tuft’s University did not solely rely on dietary history but serially measured the levels of biomarkers in blood. Long chain omega-3s in human diets are primarily derived from seafood, fish oil supplements, and foods fortified with fish oils while the shorter-chain omega-3s, like α-linolenic acid (ALA), are predominantly sourced from plants.

Adults with higher levels of n3-PUFA derived from seafood {eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)} was associated with an 18% lower risk of unhealthy aging because of lower incidence of chronic diseases that include cardiovascular diseases, chronic kidney disease, lung disease, and cancer.

Surprisingly, α-linolenic acid from plants did not offer the same protection against healthy aging as those derived from seafood (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).

The study participants were sampled from a pool of 5888 adults enrolled in the Cardiovascular Health Study across 4 centers in the US. CHS is a population-based, longitudinal study to identify the risk factors related to the onset of coronary heart disease and stroke in US adults aged 65 years and older.

The researchers recruited 2622 healthy adults at baseline with a mean age 75 years and measured plasma phospholipid n3-PUFAs at three-time points over a 13-year period (1992/93, 1998/99, and 2005/06) to account for trends over time. Researchers measured cumulative levels of plasma phospholipid n-3 PUFAs using gas chromatography and expressed it as a percentage of total fatty acids.

Sociodemographic information gathered included age, gender, ethnicity, education, and income. Risk factors measured at each visit include dietary habits and intake, alcohol intake, body mass index, physical activity (excluding chores), blood pressure, lipids, lipid-lowering drugs, and smoking status.

 Participants were also asked about self-perceived general health, family history of myocardial infarction or stroke, hypertension, osteoporosis, depression, and arthritis.

Only 10% of the study population was non-white, and the majority (64%) were women. Those with higher blood levels of long-chain n-3 PUFAs were more likely to be female, well educated, from higher income group and leading a healthier lifestyle in general and consumed an additional serving of fish as compared to those with lower levels.

At the start of the study, n-3 PUFA levels were comparable between healthy agers and unhealthy agers. During 21 803 person-years of follow-up, 2330 (89%) participants did not age well, and 292 (11%) experienced healthy aging (positive deviance).

After taking into account the various demographic, medical and lifestyle confounders, participants with the highest long-chain n-3 PUFA levels were associated with 18% lower likelihood of unhealthy aging, as compared to those with lower levels.

When the researchers analyzed for individual n-3 PUFA, they found that individuals in the highest EPA or DPA groups had 24% and 18% lower risk of unhealthy aging as compared to those in the lower group. This protection was not provided by plant-based α-linolenic acid or docosahexaenoic acid (DHA).

In linear regression models, higher levels of long-chain n3-PUFAs, but not α-linolenic acid, were consistently associated with a lower likelihood of unhealthy aging.

Yeyi Zhu, Ph.D., MS, research scientist, Division of Research, Kaiser Permanente Northern California, and assistant adjunct professor, Department of Epidemiology & Biostatistics, University of California, San Francisco noted in an accompanying editorial “fresh evidence provides clues to healthier, not just longer lives.”

However, these results come with a caveat that no conclusion about the amount of food or the role of omega-3 fatty acid supplementation can be made from the study analysis. The authors only studied the blood levels of omega-3s from seafood and found that higher levels increase the chances of living a healthy life.

An epidemiological association does not prove causality, but this study encourages further research in the role of plausible biological mechanisms and interventions related to n3-PUFAs for the maintenance of healthy aging.

According to an estimate, 28 million life-years are lost annually from ill health, disability, or early death due to inadequate omega-3 intake worldwide. In the United States (US), LC omega-3 deficiency is ranked among the top-ten preventable causes of all-cause death.

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First blood pressure monitor with cellular connectivity launched in the USA

Livongo Health, the leading consumer digital healthcare company today announced its launch of first blood pressure monitor with cellular connectivity in the U.S. at Health 2.0. It provides the simplest way to acquire, monitor and transfer the blood pressure reading to the cloud for Remote Patient Monitoring (RPM). This seamless “cuff to cloud” transfer enables the consumer to remain in the relaxed atmosphere of their home, thereby eliminating the “white coat syndrome.”

The patients also receive useful and timely insight into BP and Health Nudges TM from certified professional specially trained in the management of chronic diseases.

Just as we did with diabetes, Livongo wants to make it easier for people to stay healthy by checking their blood pressure, receiving real-time personalized feedback, sharing the information with their physician and other members of their connected care community from home, thereby avoiding a rise in blood pressure that can come with visiting a doctor," said Amar Kendale, Chief Product Officer, 

Livongo. 

"We are proud to introduce the first cellular-enabled blood pressure monitoring system to market in the U.S. and to add this capability to our comprehensive platform for people with all kinds of chronic conditions. This allows us to treat the whole person and the challenges they face seamlessly."

Livongo’s signature offerings include Livongo for Diabetes, Livongo for Hypertension, and Livongo Diabetes Prevention (DPP) powered by Retrofit.

Diabetes and Hypertension are the fastest growing chronic diseases in the United States and account for 458 billion dollars in healthcare costs. Improving the blood pressure control through lifestyle change and adherence to medication can bring down the chance of cardiovascular event by 50%.

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Is Coffee, the latest antidote for aging?

You can now stop feeling guilty about the second or third cup of coffee every morning. A new study published in Nature Medicine has shown an inverse association between caffeine intake and age related morbidity and mortality.

An inverse association exist between amount of tea and coffee consumed and long term morbidity has been suggested in many earlier studies, but the mechanism about this cause and effect relationship was not clear.

The study focused on cells of coffee drinker and non-coffee drinker and found that those who consumed high levels of caffeine tend to have lower levels of inflammation.

 Inflammasomes are protein complexes that regulate expression of interleukin-1 (IL-1) family cytokines, and are central to the regulation of a broad variety of inflammatory disease processes, A culprit responsible for many things like aging, cancer, heart disease, Type 2 DM and Alzheimer’s. 

Whole blood gene expression was measured by microarray from blood samples provided by 100 young and old people. They found that as people age they show a higher activity of Inflammasomes genes associated with the production of a circulating inflammatory protein, called interleukin-1β (IL-1-beta). Older people had significantly high levels of this inflammatory protein.

They further sub analyzed the older group, and after controlling for other confounders found out that those people who consumed at least 5 or more cup of coffee per day have the lowest level of inflammation in the body. The other groups with low caffeine intake had elevated oxidative stress, high rates of hypertension and arterial stiffness. They were also more likely to die during the 8 years of follow up of the study participants.

The researchers than isolated the protein, IL-1-beta and injected it into mice. It triggered massive systematic inflammation and arterial stiffness.

They then added IL-1-beta to human immune cells in the lab, followed by adding caffeine into the mix, too. They discovered that caffeine prevented those compounds from producing their inflammatory effects.

“The more caffeine people consumed, the more protected they were against a chronic state of inflammation,” says study author David Furman, consulting associate professor at the Institute for Immunity, Transplantation and Infection at Stanford University. “There was no boundary, apparently.”

"Most of the diseases of aging are not really diseases of aging, per se, but rather diseases of inflammation,” he further added.

The study is important because it traces novel connection between aging and chronic diseases via Inflammasomes. Inflammatory high expressors and the downward spiral towards many chronic diseases awaits further research. But, interestingly high caffeine levels were found to be associated with low expressors and protective against age related morbidity and mortality.

Further studies with large sample size are underway, till then, most of us can continue drinking coffee without feeling guilt over the second or third cup in the morning. 

Access the abstract in Nature Medicine here.

Access the Editorial published in Science Translational Medicine here.

Premenopausal Bilateral Oophorectomy accelerates aging and incidence of 18 chronic morbidities.

Clinical Pearls:

• Women who had bilateral oophorectomy before menopause experienced increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001). 
• The younger the age at oophorectomy, the stronger the association with these chronic conditions.
• In these group of women, the risk of occurrence of many chronic condition was reduced by supplementing estrogen therapy.
• Study provides definitive evidence against use of bilateral oophorectomy as a means to prevent ovarian cancer in average risk premenopausal women.

Bilateral Oophorectomy is often chosen by many  as a method for prevention of ovarian cancer in premenopausal women who are at average risk of ovarian cancer. The procedure gained popularity in US when Angelina Jolie came forward about her own experiences 2 years back.She  is a carrier of mutation in BRCA1 gene putting her high risk for ovarian and breast cancer. [1]

The current guidelines from the American College of Obstetricians and Gynecologists read, "The most effective method of preventing ovarian cancer is surgical removal of the ovaries and fallopian tubes. ...The potential benefit in cancer risk reduction for premenopausal women at average risk of ovarian cancer must be balanced with the consequences of premature loss of estrogen production."

However, in practice many doctors advise patients in favor of removal of both ovaries to eliminated the risk of  getting ovarian cancer. 

Many societies around the world have formulated guidelines so that the surgery is only performed in absolutely indicated patients like BRCA1 positive patients, but the practice still continues.

Observational studies have also documented the beneficial role of estrogen in keeping chronic morbidities at bay in women who undergo bilateral oophorectomy before the age of 46 years.

The present study was prompted because of uncertainties in the risk/benefit ratio of bilateral oophorectomy for preventing ovarian cancer and the role played by estrogen in delaying many chronic morbidities which may be sign of cellular and tissue aging.

The study was published in the recent issue of Mayo Clinic Proceedings.[2]

The researchers used the Rochester Epidemiology Project records-linkage system to recruit 1653 women who underwent bilateral oophorectomy before the age of 50 years between 1988-2007 in Olmsted County, Minnesota. Each subject was than randomly matched to a control, who was also born in the same year (±1 year), but did not have bilateral oophorectomy. They were followed up for approximately 14 years to study 18 comorbidities.

At baseline it was observed that women who underwent bilateral oophorectomy were Caucasians, less educated, had increased BMI and were heavy smokers as compared to referral women. They were also more likely to suffer from mental, Cardiometabolic and somatic disorders at the time of surgery.

Researchers used inverse probability weighting to balance the baseline risk factors and individual characteristics thereby minimizing their effects as potential confounders.

Women who had bilateral oophorectomy before menopause experienced increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001). 

The younger the age at oophorectomy, the stronger the association with these chronic conditions.

In these group of women, the risk of occurrence of many chronic condition was reduced by supplementing estrogen therapy.

The researchers proposed three possible mechanisms to explain the results of the study. Although inverse probability weighting was used to rule out confounding and bring the observational study close to RCT for interpretation as possible, genetic, environmental and lifestyle factors may have acted as confounders.

Premature and abrupt decline in estrogen levels may have led to increase in ‘epigenetic age’ serving as a bio-marker for accelerated aging.

Oophorectomy leads to loss of protective effect of other ovarian hormones progesterone, testosterone, or inhibin and disrupts the hypothalamic-pituitary axis.

The study had several strengths and limitations. As all the data was extracted electronically it eliminates the recall bias and non- participation of the subjects. Study may have underestimated those conditions which do not have any medical code, as the data was extracted form records.  Statistical power was limited for some associations for the time the women were followed. It may become significant if they are followed for longer period of time.

To Conclude, the study results along with results of the earlier studies provides definitive evidence against use of bilateral oophorectomy as a means to prevent ovarian cancer in average risk premenopausal women. Study also emphasizes the protective effect estrogen may exert to delay cellular and tissue level aging which is manifested as increased risk of multiple morbidities.  

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[1]http://www.nytimes.com/2015/03/24/opinion/angelina-jolie-pitt-diary-of-a-surgery.html?_r=0

[2] http://www.mayoclinicproceedings.org/article/S0025-6196(16)30447-5/fulltext

Moderate intensity physical activity for an hour mitigates the risk of death associated with sedentary lifestyle: A Meta-analysis.

Clinical Pearls:

• Intense to moderate physical activity for 60-75 minutes’ can eliminate the effects of prolonged sitting (> 8 hours).
• This equals to brisk walking at 5.6 km/h or cycling for pleasure at 16 km/h.

The association of sedentary lifestyle and many chronic conditions and colorectal cancer is well known and physical inactivity is an important modifiable risk factors in the causation of many chronic condition.  Prolonged sitting is one of the important cause of premature mortality.

But, according to a Meta-analysis involving about a million people, intense to moderate physical activity for 60-75 minutes’ can undermine the effects of prolonged sitting. This study was published online in the Lancet on July 27, 2016.[1] Examples of physical activity were brisk walking at 5.6 km/h or cycling for pleasure at 16 km/h.

This is a second in the series of articles published on physical inactivity by Lancet, the first was published in 2012, sending a message that physical inactivity is a global pandemic killer-responsible for 5.3 million premature deaths worldwide. The number equals the deaths caused by smoking and twice the deaths caused by obesity.

This is the first harmonized meta-analysis that compares the relationship between all-cause mortality and sedentary life style and different levels of physical inactivity.

A systematic review of literature identified about 16 studies out of which 13 were identified by the researchers as providing data on sitting time and all-cause mortality.

The combined study data generated data on pool of 1,005,791 individuals from different countries, who were followed up for 2-18 years.

The study participants were divided into quartiles according to the time spent being physically active and ranged from less than 5 minutes/day to 60-75 minutes/day. The daily sitting and TV viewing time was also divided into 4 standardized protocol.

It was seen that those who very active (60-75 minutes/day), the amount of sitting time does not increase the mortality. But, the risk of death increases as the activity time decreases. WHO guidelines also recommends at least 150 minutes of physical activity per week, which is far less than what the study recommends.[2]

"A clear dose-response association was observed, with an almost curvilinear augmented risk for all-cause mortality with increased sitting time in combination with lower levels of activity," the researchers noted.

For the purpose of estimating the hazard ratio(HR), the most active individuals were used as the reference group. (HR=1).

People who exercised the least (less than 5 min/day) were at highest risk, even if they did not spend much time sitting (less than 4 h/day). In this group the hazard of premature death was 1.27. This was way higher than those group of individuals who were most active physically (60-75 min/day) but also spent more than 8 hours sitting (HR=1.04). This was very close to the referent group, which led the researchers to conclude that physical inactivity is the root cause of premature deaths, independent of the hours of sitting.

The findings of this study emphasized the importance of physical activity, even if you have a job that demands prolonged sitting.

The study also draws attention towards relationship with TV watching and premature death. Watching TV for more than 3 hours per day is associated with premature death regardless of physical activity except in the most active quartile. In this group the mortality was only increased if you watch more than 5 hours of TV. The benefit of physical activity is not very strong in people watching TV because of “residual confounding”. Dr. Ekelund points that perhaps these people have unhealthy life- style that include snacking or drinking that increases the risks.

Ekelund pointed out in a London press conference [3]  that the average amount of time adults in the United Kingdom spend watching TV is three hours and six minutes. “I don’t know if it’s too much to ask that maybe a little of those three hours be devoted to physical activity,” he said. The general rule of thumb, as Ekelund succinctly advised: “Sit less and move more, and the more the better.”

He also emphasized the message about "moving more," suggesting that people should walk as much as they can and that if they do need to sit for prolonged periods, they should break up those periods with short bursts of activity, such as walking for 5 minutes every hour.

The full Lancet podcast about the series can be heard here.

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[1] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30370-1/fulltext

[2]  http://www.who.int/dietphysicalactivity/factsheet_recommendations/en/

[3] http://press.thelancet.com/PhysicalactivityMEDIA.mp3