Overweight, obese men at higher risk of severe liver disease, liver cancer

Men with more than normal body weight from an early age (17-19 years) are at higher risk of developing severe liver disease and even liver cancer in later life. The risk is increased when such men develop diabetes.

The association between body weight and higher risk of severe liver disease has become clear in a study based on data of more than 1.2 million Swedish men enlisted for military conscription between 1969 and 1996. Compared with men who have normal weight, those who are overweight (body mass index more than 25 kg/m²) have about 50% greater risk and obese men (BMI greater than 30 kg/m²) are more than twice likely to develop liver disease and even liver cancer in later life.

An earlier study involving nearly 50,000 men showed an association between high BMI in early age was associated with increased risk of end-stage liver disease. The study was based on data collected between 1969-70, when overweight and obesity were relatively uncommon — only 0.8% were overweight. So the study was not statistically powered to confirm an association between high BMI and increased risk of end-stage liver disease.

But a paper published today (March 21) in the journal Gut found a statistically significant association between BMI and severe liver disease. Men who have higher BMI even at an early age are at higher risk of developing severe liver disease and liver cancer as the “duration of being exposed to a high BMI” increases the risk.

Compared with men with BMI 18.5-22.5 kg/m², men with higher BMI had higher risk of severe liver disease, with the greatest risk in those with BMI greater than 30 kg/m². The non-alcoholic fatty liver disease is likely to be the “main driver” of severe liver disease in adolescent men, the study says.

Consumption of alcohol and smoking were taken into account and those who had developed alcoholic liver disease were excluded from the final analysis, but this did not change the overall finding. But the risk of severe liver disease was “highly affected” by development of type 2 diabetes during follow-up across all BMI categories.

It is well known that people with high BMI are at increased risk of developing diabetes, which in turn is associated with heightened risk of developing severe liver disease. Yet, increased risk of severe liver disease was seen even in overweight men who did not have diabetes. As the data was restricted to men, the researchers could not study the association between BMI and severe liver diseases in women. But they say that earlier studies of middle-aged women in the UK have shown found an association; but the risk was “uncertain” for younger women.

Therefore, even if the risk is increased in overweight and obese men who develop diabetes, the association of high BMI at an early age and severe liver disease at a later date “cannot solely be explained” by type 2 diabetes, the study says.

There should be targeted intervention to prevent diabetes and more than normal BMI at an early age.

Published in The Hindu on March 21, 2017

CCMB: Can alpha chain of clusterin protein control weight, fat gain in animals?

T Ramakrishna_Ch. Mohan Rao_M.Suvarsha Rao-Optimized-1

Dr. Ramakrishnan (left), Dr. Mohan Rao (centre) and Suvarsha Matukumalli studied rats injected with beta chain and found fat accumulation from day two onwards.

The two chains of clusterin protein, which are normally expressed in several tissues and can be found in several body fluids, when present together tend to lower lipid levels but administration of one of its chains — alpha or beta — results in completely different outcomes. Cells treated with a recombinant beta chain tend to accumulate fat while cells treated with an alpha chain showed no increase in lipid accumulation. Rabbits administered with a recombinant beta chain showed nearly 40% increase in weight while animals given an alpha chain showed no such increase. The results were published in the journal Scientific Reports.

“Two chains of clusterin when present together tend to decrease body weight but one of the two chains (beta clusterin) increases body weight. This is quite unusual,” says Dr. Ch. Mohan Rao from the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, and the corresponding author of the paper. “So the alpha chain should ideally be compensating for increase in body weight. But the alpha chain does not do that.”

Rats gained lean mass not fat

“While excess energy gets accumulated in the form of fat when beta chain was injected into rats, we did not see this in the case of alpha chain. One possibility is that the alpha chain helps in the metabolism of food in such a way that fat does not accumulate,” he says. “Dissected rats that were given alpha chain showed increased levels of lean mass.”

Apparently, there was no difference in the food intake between animals treated with alpha or beta chain. “It means that weight increase can happen even when there is no increase in food intake. It is the energy management by the body that is important. And alpha chain seems to modulate metabolism in such a way to promote energy expenditure and thus prevent fat accumulation,” he says.

The effect of alpha and beta chains were tested on myoblast cells, fibroblast and cancer cells. The individual chains were injected into rabbits as well. “In my lab we study the effect of small heat shock protein on health and disease. To raise antibody for clusterin we injected the chains separately into rabbits. One set of rabbits was gaining weight while the other did not. That’s when we investigated the reasons. The animal-house in-charge noticed the change in the animals,” recalls Dr. Rao.

Rats too gained weight

Though the effects of the two chains were seen in rabbits, the researchers turned to rats as more animals were required for investigating the effect of individual chains on animals.

“We could see fat accumulation in cells from day two onwards. We observed for 10 days and fat accumulation continued for all the 10 days; we could study cells continuously only for 10 days,” says Suvarsha Rao Matukumalli from CCMB and the first author of the paper. “In the case of animals injected with beta chain, fat accumulation continued for four-five months. The controls and animals given alpha chain did not show weight or fat gain.”

When cells were administered both the chains simultaneously, the cells did not accumulate fat for two-three days but started thereafter. “Fat accumulation was not as much as when only the beta chain was given but fat accumulation nevertheless continued,” says Ms. Matukumalli. But the effect of both the chains in animals was quite different. “When we introduced both alpha and beta chains together in animals we did not see any weight gain. The animals were very much like the controls,” she says. “Only large-scale, in-depth studies can reveal if alpha chain prevents weight gain.”

Published in The Hindu on March 19, 2017

Higher abdominal obesity triples breast cancer risk in Indian women


Higher abdominal obesity was found to be responsible for all types of breast cancer in Indian women. – Photo: R. Prasad

Immaterial of their menopausal and hormone receptor status, Indian women who have a high waist-to-hip ratio (central obesity) of over 0.95 have three times higher risk of breast cancer than those who have waist-to-hip ratio of less than 0.84, according to a study published on August 30 in the European Journal of Cancer. The association was found even after body mass index (BMI) effect was adjusted.

Studies have already found that BMI is consistently associated with increased risk of breast cancer in postmenopausal women but decreased risk for premenopausal in Caucasians and Asian population. And central obesity or abdominal obesity — excessive abdominal fat around the stomach and abdomen — has also been associated with increased risk of breast cancer in postmenopausal women but its effect on premenopausal women varies in different ethnic groups.

“Breast cancer is a heterogenous disease but in our study we found that abdominal obesity was responsible for all types of breast cancer in both premenopausal and postmenopausal women. In fact, there is nearly three times increased breast cancer risk in women who have high central obesity,” says Dr. Rajesh Dikshit, the corresponding author of the paper from Tata Memorial Centre, Mumbai, India.

Higher abdominal obesity might be the reason for increasing trend in breast cancer cases in urban areas.The second important finding of the study was that even in those with normal BMI but high abdominal obesity, the risk of breast cancer was three times higher. “In India, it is common to see people with normal BMI having high central obesity.  So BMI is not a sensitive marker for obesity in the Indian ethnic population,” he says. This has been seen in several diabetes-related studies as well.

Another interesting finding of the study was the association of low BMI but higher abdominal obesity and increased risk of breast cancer irrespective of the menopausal status. It is well known that Indians with even low BMI have high abdominal obesity.  In the study, nearly 18 per cent of controls had low BMI but a high wait-to-hip ratio.

“Most Indian women have low birth weight and higher weight at age 20 years. An increase in body size from age 10 to 20 years is thus indicative of accelerated growth in childhood which may result in increased adiposity and insulin resistance influencing breast cancer risk,” they write.

“Obesity is associated with inflammatory response, and inflammatory response, in turn, starts the cell proliferation process,” Dr. Dikshit says. The greater the cell proliferation, the greater the chances of something going wrong and cancer setting in.

Abdominal obesity

Even women with a normal BMI have higher abdominal obesity in India.

The number of women with breast cancer in urban areas is twice that of rural areas. “Breast cancer trend is increasing in the urban areas.  Central obesity could be the reason,” Dr. Dikshit says. The good news is that abdominal obesity can be controlled thereby reducing the risk of breast cancer.

The study was carried out in 1,633 breast cancer patients and 1,504 controls who visited Mumbai’s Tata Memorial Centre between 2009 and 2013. The researchers measured BMI, waist-to-hip ratio and other anthropometric measurement at the time of enrolment. The participants were then shown a pictogram for body size at different ages and asked to recall their body size and chose the pictogram that best depicted their size. Pictograms were used to understand the increase in body size at two stages — from age 10 to 20 and from age 20 to age at the time of enrolment.

“We found very good correlation between pictogram and current BMI. So if we see a sudden increase in weight between age 10 and 20 then there is higher breast cancer risk,” he says, explaining how the pictogram was used in the study.

“Our study is suggestive as it relies on recall. But that’s the only way to carry out the study as otherwise we must wait for 40 years to complete it,” he adds.

Published in The Hindu on September 5, 2016

Using fat tax to change food consumption behaviour

Using tax as a tool to alter consumer food preferences has been recommended by the World Health Organisation. Mexico provides us with proof that levying additional taxes on non-essential food items that are rich in fat or calories can effectively alter food choices. The country witnessed a 5.1 per cent dip in consumption levels in foodstuff that had more than 275 kcal/100 g energy density following the imposition of an 8 per cent levy in 2014. Sugar-sweetened drinks saw a 12 per cent drop in intake at the end of the very first year the tax was introduced. In this context, Kerala’s decision to slap a 14.5 per cent tax on certain calorie-rich food items such as pizzas, doughnuts and pasta sold in branded restaurants may seem like a step in the right direction. But it bears the stamp of being little more than a political gimmick. For once, such foods sold by branded restaurants, consumed by the higher middle and upper classes, are a very tiny part of the problem of poor food choices for the State’s population. Ignoring a wide variety of high-calorie food items and focussing on a few is no more than tokenism. The revenue that Kerala hopes to mop up from this — Rs.10 crore — is also meagre.

Taxing ‘bad’ foods should be accompanied by cross-subsidies of healthy and wholegrain food items.

If the State is serious about reining in consumption of unhealthy food, then there are several measures it should quickly adopt.The first is to set a threshold limit for fat and/or calorie and tax all foods items that are above this limit. Bringing sugar-sweetened drinks and refined products under the taxable product list should be a priority. There is no reason why packaged food items that have high salt content should not be additionally taxed. Indians are known to consume a few times more than the WHO’s recommended limit of 5 grams a day and most of it comes from packaged food items. Similarly, what excuse can there be for not charging a very high rate of tax on food items that contain trans fats? There are a number of food items sold in India that contain as high as 35-40 per cent of trans fats. Trans fatty acids, made through the process of hydrogenation of oils, which improves the stability or shelf life of the foodstuff that contains them, pose serious coronary risks. Taxing ‘bad’ foods should be accompanied by cross-subsidies of healthy and wholegrain food items. Only a holistic approach such as this will be effective in making a real change in our food consumption behaviour. At the same time, the food industry too should play a significant role in promoting healthy diets.  According to the WHO, the food industry can “reduce the fat, sugar and salt content of processed foods, ensure that healthy and nutritious choices are available and affordable to all consumers, and restrict marketing of foods high in sugars, salt and fats, especially those foods aimed at children and teenagers.”

Published in The Hindu on July 13, 2016

Is Kerala’s fat tax a mere topping than health initiative?



Kerala’s bold step to levy fat tax on certain junk food items appears to mirror the Denmark example.

In a bold step that might have a positive impact on public health, Kerala has become the first State in the country to introduce a 14.5 per cent tax on burgers, pizzas, donuts, sandwiches and pasta sold through branded restaurants. Introducing additional tax on fat-rich food products has been tried out in other countries with varying degrees of success. Where Denmark has failed, will Kerala’s experimentation succeed?

The answer to that question depends on what the objective is. Unfortunately, the rationale behind the move has not been spelt out except that it will bring in additional Rs.10 crore to the government’s coffers.

There is a strong case to bring in several measures to tackle the burgeoning waistline of school children and adults in Kerala. For instance, a June 2012 study (Indian Pediatrics) of 1,634 children between 6-15 years from three urban schools in Kochi, Kerala, found the prevalence of obesity among boys to be 3 per cent and 5.3 per cent for girls and the prevalence of overweight was 10.2 per cent in boys and 12.1 per cent in girls. An April 2014 study of 1,098 school children in the rural areas of Kochi district found 9 per cent of girls and nearly 6 per cent boys were overweight while 2.8 per cent girls and 3.3 per cent boys were obese.

Levying a tax on calorie-rich, unessential food items and beverages has been the preferred route to rein in consumption of unhealthy products and as a means to change consumer behaviour in some developed countries. Hungary taxes food high in fat and sugar, France taxes soft drinks and Mexico levies tax on junk food and sugar-sweetened beverages, while 34 U.S. States and the district of Columbia have food taxes that affect sugar-sweetened  drinks.
The food items have not be chosen based on energy density or fat content threshold. So,  numerous high calorie, fat-rich food products have been left out.

In October 2011, Denmark became the first country in the world to introduce a tax on saturated fat. Tax was levied on all foods that contained more than 2.3 per cent fat, including milk, butter, cheese, oil, and meats, as well as frozen pizzas and other processed foods. However, it was repealed by the end of 2012 even before tax on sugar-sweetened beverages could be introduced. Similarly, in Mexico, where prevalence of overweight and obesity is over 33 per cent in children and about 70 per cent in adults, 8 per cent tax was introduced on all nonessential food items with energy density of more than 275 kcal/100 g and 10 per cent on all sugar sweetened beverages since January 2014.

In contrast, the focus in Kerala has been only a few calorie-rich, nonessential food items for additional taxation and is not based on any cut-off energy density or fat content. As a result, numerous energy-dense, fat-rich food products have been left out. It is also surprising that sugar-sweetened beverages have been excluded from the list of taxed products. In January 2016, the World Health Organisation had urged governments to levy additional taxes on sugar-sweetened beverages to end childhood obesity.

According to a study (Health Policy, June 2015), in Denmark, the fat tax was considered as a “source of funds for the tax reform rather than a public health initiative”.  The taxation rate was “adjusted to yield certain tax revenue rather than a certain health benefit,” the tax did not reflect the actual content of saturated fat in a product and the tax was processed by the Ministry of Taxation and not the Health Committee. Still, consumption of saturated fat items reduced by 10-15 per cent due to the tax (Food Policy, October 2013); an April 2016 study pegs the reduction in intake at 4 per cent. Kerala’s case seems very similar to that of Denmark.

On the other hand, Mexico has shown that a well-thought-out strategy focussing primarily on reducing unhealthy food consumption can yield rich dividends. During the first year of taxation in 2014, a January 2016 paper in the medical journal BMJ says that there was a 12 per cent reduction in sugar-sweetened beverages intake, while a PLOS Medicine study (July 2016) noted a 5.1 per cent drop in the consumption of energy-dense food items.

Results from Mexico also show that while no change in consumption pattern was seen in high socio-economic status households, a 10.2 per cent and 5.8 per cent reduction in the consumption levels was seen in low and medium socio-economic status households respectively. This is not surprising as low-income populations are more sensitive to price changes. However, in the case of Kerala, the prime target is the middle and high socio-economic households. Still, in all probability, the exercise will bring about a change in the consumption pattern as the fat tax is way higher than even Mexico’s.

The outcome of Kerala’s exercise will be keenly watched by other States. The war on obesity and many chronic health diseases caused by fat-rich food intake can be won if Kerala can pull it off by undertaking certain mid-course corrections and not go the Denmark way.

Sin tax reduces intake of energy-dense food in Mexico


After the introduction of sin tax, 25 grams per person per month reduction in intake of energy-dense food was seen in Mexico.

That taxing energy-dense, unhealthy food will result in a drop in consumption levels has come out unequivocally clear in Mexico. In January 2014, Mexico introduced 8 per cent tax on foods items with energy density of over 275 kcal/100 g and one peso per litre of sugar-sweetened beverages.

Data of household consumption of nonessential energy-dense food in Mexico shows a decline in 2014. The nonessential food included salty snacks, chips, pastries and frozen desserts.  The results of a study were published on July 5, 2016 in PLOS Medicine.

While there were no changes in mean volume of purchase of taxed food items among high socioeconomic status households, both low and medium socioeconomic households showed a reduction. The reduction was 10.2 per cent in the case of low socioeconomic households, while the drop was 5.8 per cent in the case of medium socioeconomic households. Compared with households from higher socioeconomic status, the low socioeconomic households bought less taxed food before and after tax but showed the “greatest response” to the tax. An earlier study showed a 6 per cent decline in taxed sugar-sweetened beverages.

The mean volume of purchases of taxed food during 2014 dropped by 25 grams (5.1 per cent) per person per month. The reduction of 25 grams per person per month translates into 70-110 kcal. However, there was no change in the purchase of non-taxable food items during 2014. The greatest change in total purchase of taxed food was seen in salty snacks and cereal-based sweets.

The purchases represent only a “fraction” of all household purchases, so the real absolute change in energy consumption from taxed food products “might be higher”, the authors say.

Besides reducing the amount of energy-dense food consumed by individuals, the introduction of taxes had an unexpected positive impact. Many companies reformulated their products, particularly jam and spreads, to fall under the 275 kcal/100 gram threshold.

The study used data on volume of household food purchases between January 2012 and December 2014 and included 6, 248 households.

Mexico introduced the tax as it has one of the highest prevalence rates for overweight and obesity in the world at over 33 per cent for children in the 2-18 years age group and around 70 per cent for adults. In 2006, the prevalence of diabetes in adults was 14.4 per cent. Mexico is the fourth largest consumer of energy-dense, ultra-refined food and drinks.

Published in The Hindu on July 6, 2016

One minute of hard exercise thrice a week has great health benefits

“I don’t have the time to exercise” can no longer be an excuse. A single minute of very intense exercise per week can produce similar health benefits as 45 minutes of continuous, moderate-intensity cycling a week, a study found.  Even the one minute exercise was split into three short bouts of 20 seconds separated by two minutes of low-intensity cycling.  The results were published on April 26 in PLOS ONE.

Jenna B. Gillen, the first author of the paper from McMaster University, examined key health indicators including cardiorespiratory fitness and insulin sensitivity, a measure of how the body regulates blood sugar, to see the difference in exercise duration and intensity and health benefits.

For the 12-week study, 27 sedentary men were recruited and assigned to perform three weekly sessions of either intense or moderate training; a control group did not exercise.

The intense cycling — sprint interval training (SIT) — protocol involved three 20-second “all-out” cycle sprints.  The volunteers warmed up for two minutes and then pedalled hard for 20 seconds and then pedalled slowly for two minutes and then repeated the cycle of hard pedalling and slow pedalling two more times. At the end the three 20-second bouts, the volunteers cooled down for three minutes.  The entire workout duration lasted only for 10 minutes.

Volunteers in the moderate-intensity continuous training (MICT) group warmed up for two minutes and then pedalled continuously for 45 minutes and then cooled down for three minutes. The entire duration of exercise lasted 50 minutes.

Cardiorespiratory fitness

At the end of the study, brief but intense exercise improved cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite the duration of exercise and time spent being five times lesser, the study found. Though it was known that brief hard workout increased cardiorespiratory fitness, there has been no study to conclusively prove it by comparing it with long-duration moderate exercise.

While an earlier study found that low-intensity exercise for 150 minutes per week for over 24 weeks may not be sufficient to improve cardiorespiratory fitness of many adults, the present study found that in sedentary adults, a meagre three minutes of exercise per week of short, intense burst of exercise within 30 minutes duration over 12 weeks can bring significant improvement.

The researchers are not sure of the precise mechanism that is responsible for the improvement in both the arms that did exercise.

Insulin sensitivity

Similarly, the insulin sensitivity index increased 53 per cent in those doing intense exercise compared with 34 per cent for those exercising for 45 minutes per session.

Earlier studies have shown that for a given energy expenditure, higher-intensity exercise confers greater benefits than moderate-intensity exercise, especially in people with obesity, metabolic disorders, and Type 2 diabetes. The present study strengthens this observation.

Compared with the control group, both the groups that exercised improved their peak oxygen uptake by 12 per cent after six weeks of exercising.  The peak oxygen uptake increased to 19 per cent after 12 weeks of training versus pre-training.  Though body mass remained for people in all the three groups (two exercise groups and control), there was a reduction in the percent body fat in people who exercised.

“If you are an elite athlete, then obviously incorporating both endurance and interval training into an overall program maximizes performance. But if you are someone, like me, who just wants to boost health and fitness and you don’t have 45 minutes or an hour to work out, our data show that you can get big benefits from even a single minute of intense exercise,” Martin J. Gibala, the senior author told The New York Times.


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Editorial: Brief workouts matter