By Abigail Klein Leichman
A drug that melts body fat and a nasal insert that curbs appetite are among the Israeli innovations contributing to the fight against obesity.
Obesity is one of the biggest killers of the modern world due to the many diseases it causes. The World Obesity Federation predicts there will be 2.7 billion overweight and obese adults by 2025, about one-third of the global population.
Three years ago, the World Health Organization introduced World Obesity Day, October 11, to stimulate and support practical solutions to help people achieve and maintain a healthy weight and to reverse the obesity crisis.
Defined as a body mass index (BMI) of 30 or more, obesity has nearly tripled since 1975 and the numbers are rising – even in countries such as Israel where overweight is a relatively new phenomenon.
This trend worries Dr. Dror Dicker, head of the Obesity Clinic at Hasharon Hospital-Rabin Medical Center in Petah Tikva, president of the Israeli Association for the Study of Obesity and co-chair of the Obesity Management Task Force of the European Association for the Study of Obesity.
He does have some promising perspectives on progress being made in Israel, however.
“In the disease area, we understand the physiology much more and we have more efficient tools than we had five years ago,” says Dicker. “There is a lot of research in Israel regarding bariatric surgery; the relationship between gut hormones and weight loss; the contribution of physical activity to weight loss; the function of the fat layer; and the effect of different diets on different layers of body fat,” he adds. “We now know that there isn’t one treatment that fits all; we have to understand the individual’s metabolism and microbiome.”
At the international ObesityWeek conference in Nashville this November, Dicker will speak about Israeli bariatric surgery, whose cost is covered by national health insurance.
“We lead the world in the number of bariatric surgeries per capita. For the right patient it’s a game-changer, but they have to be followed up for the rest of their lives to prevent regaining the weight,” he says.
Dicker explains that maintaining weight loss – no matter how it was accomplished – is extremely difficult because of a physiological mechanism that interprets the fat reduction as a threat to the body’s ability to produce energy.
Prevention is the best remedy for the obesity crisis, Dicker says. Israel is taking pioneering steps such as a red label that will be required as of January 2020 on prepackaged retail foods containing high amounts of sodium, sugar and/or saturated fat.
Below are 10 Israeli advances in preventing, understanding and treating obesity.
Dicker was the principal investigator in a clinical trial of NozNoz, a drug-free nasal insert worn during the day to reduce appetite by diverting incoming smells away from olfactory receptors in the nose.
“Smell has a strong connection to metabolic function,” says Adva Beck, CEO of Beck Medical in Givat Ada outside Tel Aviv.
Food odors cause cravings and also stimulate the olfactory bulb to release hormones that affect feelings of hunger and satiation, as well as glucose and fat management, she explained.
The soft insert is sold online as a non-medical weight-assistance wellness device to customers in the European Union, United States and Israel.
- A drug that melts fat
Jerusalem-based Raziel Therapeuticsis developing an injectable drug to correct the imbalance caused by consuming more calories than the body normally can burn.
The drug generates heat from the fatty acids produced by fat cells, melting away those cells and postponing the proliferation of new fat cells.
Raziel’s first clinical trial in the USA showed a 30-50 percent reduction in subcutaneous fat at the treated site after one injection, with effects lasting several months. CEO Alon Bloomenfeld expects that the injection eventually will be available in physicians’ offices.
The pharma company currently is carrying out two Phase IIA clinical studies in the United States, one focusing on the drug’s effectiveness against obesity and the other on its effectiveness against Dercum’s disease, a rare disorder that causes painful growths of fatty tissue called lipomas.
“We see that most of the lipomas are gone after one treatment,” explains Bloomenfeld.
- Zen Eating
Inventor Scott Hirsch of Jerusalem learned that his sleep apnea stemmed from improper swallowing. He devised a simple tool to correct this problem and then discovered that he was also feeling full from less food.
Launched in March 2018, Hirsch’s Zen Eating patented BPA-free silicone sipping device — available online with free international shipping and money-back guarantee – is used for five seconds before a meal to train your tongue and throat to swallow smaller amounts at once.
“Overeating starts with over-swallowing food,” says Hirsch, citing studies showing that proper swallow training can prevent obesity.
“Over-swallowing triggers a small stress response. It also leaves a big oral space that gets filled with too many calories per gulp. Both of these in turn encourage under-chewing food.”
Swallowing smaller amounts automatically slows eating and increases chewing, he says. “It makes it easy to get into the proven weight-loss habit of eating a meal in 20 minutes instead of the average of nine,” giving the body enough time to feel satiated so that you will eat up to 30 percent less per meal.
- CBD vs. fatty liver cells
The Multidisciplinary Center on Cannabinoid Research of the Hebrew University of Jerusalem received funding earlier this year from CIITECH, a UK-Israel cannabis biotech startup, for studies using cannabis plant extract cannabidiol (CBD) to treat non-alcoholic fatty liver disease.
This common and potentially serious condition affects up to 80% of obese people.
Lead researcher Dr. Yossi (Joseph) Tam heads the center and the university’s Obesity & Metabolism Laboratory, which studies the role of the endocannabinoid system in obesity and its metabolic implications.
CBD has been shown to modulate fatty acid accumulation in the liver and inhibit weight gain in rats on high-fat diets.
“We know CBD is potentially able to elicit positive metabolic effects under fatty conditions such as an unbalanced diet. What we’re exploring in this study is whether CBD and other non-psychoactive cannabis compounds can either diminish, inhibit or reverse the growth of fatty liver cells and even prevent their development,” said Tam.
- High-energy breakfast promotes weight loss
People with obesity and type 2 diabetes can benefit from eating a high-energy breakfast, according to a recent study led by Dr. Daniela Jakubowicz, professor of medicine at Tel Aviv University.
“This study shows that, in obese insulin-treated type 2 diabetes patients, a diet with three meals per day, consisting of a big breakfast, average lunch and small dinner, had many rapid and positive effects compared to the traditional diet with six small meals evenly distributed throughout the day: better weight loss, less hunger and better diabetes control while using less insulin,” she said.
“The hour of the day — when you eat and how frequently you eat — is more important than what you eat and how many calories you eat,” she noted when presenting the results at the 100th annual meeting of the Endocrine Society in Chicago last March.
“Our body metabolism changes throughout the day. A slice of bread consumed at breakfast leads to a lower glucose response and is less fattening than an identical slice of bread consumed in the evening,” she said. “A diet with adequate meal timing and frequency has a pivotal role in glucose control and weight loss.”
- Gut microbiomes and yoyo obesity
An Israeli study published in Nature revealed that altering the composition or function of the intestinal microbes (gut microbiome) in lab mice that had been obese and lost weight, prevented the common weight-cycling phenomenon known as “yoyo obesity.”
“We’ve shown in obese mice that following successful dieting and weight loss, the microbiome retains a ‘memory’ of previous obesity,” said co-lead researcher Eran Elinav of the Weizmannn Institute of Science in Rehovot. “This persistent microbiome accelerated the regaining of weight when the mice were put back on a high-calorie diet or ate regular food in excessive amounts.”
The scientists developed a machine-learning algorithm that accurately predicted the rate of weight regain in each mouse, based on the characteristics of its microbiome after weight gain and successful dieting. They also identified two flavonoid molecules involved in weight cycling.
“By conducting a detailed functional analysis of the microbiome, we’ve developed potential therapeutic approaches to alleviating its impact on weight regain,” added Prof. Eran Segal.
- Obesity lowers effectiveness of flu vaccine
Ben-Gurion University of the Negev researcher Tomer Hertz was one of the researchers in a 2016 study at St. Jude Children’s Research Hospital in the United States that showed that flu vaccines do not work as well in obese mice as in lean mice. The findings, published in the scientific journal mBio, suggest that obesity makes individuals vulnerable to serious flu-related complications.
“We found that the antibody responses of the obese mice were not only weaker, but also less broad — recognizing a smaller set of influenza epitopes. This demonstrates that obesity also had a direct effect on the vaccine-induced antibody response,” said Hertz.
- Teen obesity raises later heart attack risk
A major database study of 2.3 million Israeli teenagers examined from 1967 through 2010 found a clear association between elevated BMI in late adolescence and subsequent cardiovascular mortality in midlife.
Published in the New England Journal of Medicine, the findings “appear to provide a link between the trends in adolescent overweight during the past decades and coronary mortality in midlife,” said Prof. Jeremy Kark of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine.
While overweight adolescents tend to become overweight or obese adults more prone to cardiovascular disease, it’s also possible that early obesity could worsen the effects of associated metabolic abnormalities later on, such as high blood pressure, impaired glucose metabolism and insulin resistance.
- Turn off the lights
A University of Haifa study published in the International Journal of Obesity suggests that sleeping in the dark helps control weight gain.
Artificial light at night (ALAN) – especially from white LED bulbs – led to body-mass gain among mice in the Israeli study. ALAN may suppress the normal nighttime production of melatonin, a hormone responsible for metabolic function.
The study considered ALAN data and obesity data from more than 80 countries. Even after adjusting for variables such as the country’s average birthrate, dietary patterns, gross domestic product and percentage of urban population, ALAN emerged as significant positive predictor for obesity.
- Obesity could trigger Crohn’s and MS
Autoimmune disease researchers at Tel Aviv University published a study in Autoimmunity Reviews showing that obesity can help trigger and prolong autoimmune diseases such as Crohn’s disease and multiple sclerosis.
The study by Prof. Yehuda Shoenfeld suggested that obesity leads to a breakdown of the body’s protective self-tolerance, creating the optimal environment for autoimmune diseases, and generates a pro-inflammatory environment likely to worsen the disease’s progression and hinder its treatment.