All Posts by ScienceToLiveBy

Genes, Obesity, and the Snowball Effect.

In The Secret Life of Fat, Sylvia Tara documented the effects of genetics on one’s propensity to gain weight and difficulty to lose it, all else being equal. (In fact, her personal experiences with these effects are what motivated Dr. Tara to investigate the genetics-fat link in the first place.)

Recent research, led by David Meyre at McMaster University, has found nine genes that combine into what the researchers call the snowball effect.

“These genes,” Meyre told Science Daily, “may, in part, explain why some individuals experience uncontrolled and constant weight gain across their life, despite the availability of different therapeutic approaches.”

This is fascinating and important research that highlights the genetic pre-disposition to obesity and points at future models to detect genes and work towards individualized lifestyle programs to prevent obesity.

We caught up with Dr. Meyre to find out more.

ScienceToLiveBy: What specifically motivated this study into the genetics of obesity?

Dr David Meyre: While the average body mass index has reached a plateau in Western countries such as the United States, extreme forms of obesity are still on the rise. The origins of super obesity are still poorly understood (is it genes, environment, both?).

This is the reason why we studied the effects of 37 well-established obesity genes on body-mass index in 75,230 adults with European ancestry using innovative statistical methods (conditional quantile regression and meta-regression models).

We found that nine of the 37 genes (24%) make individuals gain more weight if they already have a high body mass index. The effect of these genes is amplified by four times, if we compare the 10% of the population at the low end of the body mass index, compared to the 10% at the high end. The plausible explanation is that there are interactions between these snowball obesity genes and risk environmental factors.

STLB: Explain the “snowball” effect? Is that a snowballing of the number of these nine genes that an individual has? Or having all nine means the higher your BMI gets, the faster it will continue to increase?

DR MEYRE: The number of bad copies (0, 1 or 2, one inherited from your father, one inherited from your mother) for each of these 9 genes is determined at conception. It can be comprised between 0 and 18 obesity risk copies depending on the individual.

Your second proposition is right. The bad copies at these genes make you gain weight, and when you get heavier, they make you gain even more weight (a vicious circle or snowball effect). The effect of these genes on weight gain can be four-times stronger if you compare the 10% lighter and 10% heavier people.

STLB: Are there certain individual or subsets of the nine genes identified that combine for part of the effect — or is it all nine that have to work together?

DR MEYRE: The nine genes do not interact with each other, so their effect is independent and sums up. The more obesity risk copies of the genes you inherit from your parents (from 0 to 18), the more you gain weight.

STLB: Is there an available way individuals can screen for these genes, these SNPs?

DR MEYRE: The effects of these nine genes is modest (it may contribute to 2% of body mass index variation in population) so genetic testing is not relevant for now. However, genetic testing of these snowball obesity genes may become relevant when we identify all of them (there are probably several hundred snowball genes disseminated on the whole genome). This may take couple of years.

STLB: What treatments, if any, do you see that could be developed based on knowing these all these genes and the snowball effect?

DR MEYRE: Prevention may be a more adequate option here. We already know that certain of these snowball obesity genes interact with lifestyle factors such as your diet, physical activity, sleeping habits, soda and alcohol drinking consumption habits.

The strategy in the long run may be to identify the subset of people who cumulate many of these snowball obesity early in life, and to propose a personalized lifestyle intervention program based on the genetic profile that minimizes the effect of these genes and maintains individuals in the low body mass index range.

STLB: What studies do you have planned to follow up on or compliment this study?

DR MEYRE: The next step is to generalize our discoveries in populations with non-European ancestry. More than 270 obesity genes have been recently identified in European, East Asian, South Asian, African, Native North American, South American and Pacific Islander populations, and more snowball obesity genes are likely to be found in the future.

We are also developing novel statistical and informatics methods to screen the entire human genome to track-down novel snowball obesity genes. Another important goal is to identify the specific lifestyles that interact with the snowball genes. The next steps are to improve the prediction, prevention and care of snowball obesity at the population level.

The paper and abstract are available here. Read more about Dr. Meyre’s research here.

Microbiome and disease: infant risk for asthma may be more than genetic.

As readers are aware, here at ScienceToLiveBy.com we take the gut microbiome very seriously. And we’re particularly interested in how the microbiome is linked to disease. We are continuously learning how diet and behavior can influence the microbiome and health outcomes.

Late last year, a University of Alberta study showed that the family risk for asthma, usually passed from mothers to babies, may be caused by more than genetics. The study, led by Anita Kozyrskyj, found a significant reduction of the Lactobacillus family of microbes in Caucasian baby boys born to pregnant women who had asthma. According to the findings, there is strong evidence that maternal asthma during pregnancy may be associated with an infant’s gut microbes.

Dr. Kozyrskyj told Science Daily, “Our discovery, with more research, could eventually lead to a preventative approach involving modifying the gut microbiome in infants to reduce the risk.”

The lab is also looking into whether certain sex-specific risks towards being overweight are related to changes in infant gut microbiomes. We caught up with Dr. Kozyrskyj of University of Alberta to find out more about their research.

ScienceToLiveBy: What specifically motivated the research into the gut microbiome – asthma link? Had you pursued other links prior to this study?

Dr. Anita Kozyrskyj: I was motivated to study the gut microbiome-asthma link by the well-established fact that maternal asthma affects infant birth weight in a sex-specific manner. Some of this evidence was published by Dr. Clifton at the University of Adelaide.

STLB: Any hypotheses as to how gender differences may be causing the sex-specific effects on gut microbiome?

DR. KOZYRSKYJ: Male fetuses and those of mothers with asthma are more likely to have problems swallowing amniotic fluid, which is essential for intestinal absorption of nutrients. Lactobacilli have been detected in amniotic fluid.

STLB: Other coverage of your research cautioned against pro-biotic treatments, did you mean in the infants after birth, or for women with asthma before or during pregnancy?

DR. KOZYRSKYJ: I believe the article stated that it was too early for parents to act on my findings. Certainly lactobacillus-containing probiotics have been tested during pregnancy and in the infant after birth for their effectiveness in reducing onset of allergic disease. Probiotic efficacy is strongest in preventing allergic eczema and weakest in preventing asthma from developing. However, it’s possible that lactobacillus supplementation efficacy is sex-specific.

STLB: Are you looking at other gut-gender-disease links in pregnancy?

DR. KOZYRSKYJ: Male infants who are treated with antibiotics are more likely than girls to become overweight. We are also looking into whether this sex-specific risk for overweight is related to changes to infant gut bacteria.

STLB: What studies might you be planning for follow up?

DR. KOZYRSKYJ: The plan is to link these findings to the development of allergic disease in the CHILD birth cohort as children get older. CHILD cohort children are currently being assessed at age 5 for the presence of asthma and allergies.

Journal Reference:

  1. Petya T. Koleva, Hein M. Tun, Theodore Konya, David S. Guttman, Allan B. Becker, Piush J. Mandhane, Stuart E. Turvey, Padmaja Subbarao, Malcolm R. Sears, James A. Scott, Anita L. Kozyrskyj. Sex-specific impact of asthma during pregnancy on infant gut microbiota. European Respiratory Journal, 2017; 50 (5): 1700280 DOI: 10.1183/13993003.00280-2017

 

Probiotic berries

Probiotics: The year in review

It’s that time of year to start looking back and wrapping up the news — good or bad — in our favorite research areas.

What happened in the world of Probiotics in 2017?

Perhaps our favorite development comes from the National University of Singapore (NUS). As reported in Science Daily, the NUS has developed a specialty beer that incorporates the probiotic strain Lactobacillus paracasei L26. This friendly organism helps regulate the immune system and has the ability to neutralise toxins and viruses.

We can imagine the marketing — “Tastes Great!” “Less Toxins.” Okay, you have to be a certain age to remember the iconic “Tastes Great – Less Filling” Miller Lite ads. (In all fairness to us, they did bring back the tagline as recently as 2008 )

Creating the beer wasn’t as easy as you might think. Acids in beer kill off bacteria, so the brew process needed tweaking and trial and error with different strains of bacteria robust enough to survive. As of August, the student entreprenuers did not have a commercial agreement, but we’ve heard that a Japanese beverage company was interested.

Next up: allergies.

As any sufferer knows well, seasonal allergies disturb your sleep, lower productivity at work, home, and school, cause stress and embarrassment. In summary, they make life miserable.

And current allergy medications have fun side effectslike dry mouth and drowsiness. Yay!

Probiotic BerriesIn March we learned of research at the University of Florida that showed promise in relieving the symptoms of hay fever. A double-blind, placebo-controlled, parallel, randomized clinical trial, showed that a combination probiotic improved “rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies.”

Translation: allergy sufferers felt better!  Something to try out next spring.

Guts, brains, and IBS depression.

A study released in May added to the data on the microbiota-gut-brain axis, providing evidence that bacteria affect behavior.

Say the researchers, “This study shows that consumption of a specific probiotic can improve both gut symptoms and psychological issues in IBS.”

How does it work to reduce depression? Researches used fMRI to asses brain activation patterns, and measured fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. The probiotic reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions. The improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity.

That is, the priobiotic not only improve the gut, but directly improve negative brain symptoms.

High blood pressure.

An MIT study showed how a strain of intestinal bacteria can stop a high-salt diet from inducing inflammatory response linked to hypertension.

Before we get into it, this is not a license to eat fast foods and take a probiotic antidote!

Rather, if you have been enjoying a too high-salt diet then in addition to changing it, you could add the right probiotics to further protect yourself from the effects.

Yogurt and berriesSo what’s going on? Well, a high-salt diet shrinks the population of a certain type of beneficial bacteria. As a result, pro-inflammatory immune cells grow in number. These immune cells have been linked with high blood pressure, although the exact mechanism of how they contribute to hypertension is not yet known. In the study, the probiotic Lactobacillus murinus lowered the immune cell populations and hypertension was reduced.

Again, the obvious conclusion here is to avoid a sustained high salt diet. But this study and others like it reinforce the important links between diet, gut microbiome, and disease.

Age and microbiota.

At least two studies looked at changes in gut microbiota and how this relates to aging.

In one study, the researches transplanted the microbiota from the guts of old mice into young mice, causing inflammatory responses in the young mice. Inflammatory response are linked to age-related conditions such as stroke, dementia and cardiovascular disease.

Why aging tends to lead to negative imbalence in “good” and “bad” bacteria is not fully known. But the study suggests such imbalance may be on the cause side rather than the effect side of some of the inflammatory conditions that lead to age-related diseases.

Another study of “ridiculously healthy” elderly subjects confirmed that they have the same gut microbiome as healthy 30-year olds. Researchers could not identify whether this is cause or effect — do healthy elderly have good microbiomes or do good microbiomes keep people healthy into old age — but it does show that microbiome could at least be a marker for predicting health into old age or even lead to treatments for age-related conditions.

Too much of a good thing?

Before you pile on the probiotics to your already healthy diet, make sure you’re not overdoing it.

A study at the University of New South Wales exploring the link between gut health and brain function had one surprising result. For the subjects (aka rats) put on a poor diet, the diet caused memory and other brain issues. And, the good news, the probiotics helped stop the losses. That’s the good news.

But — there’s always a but — rats in the “healthy-diet” group not only saw little additional benefit to added priobitocs, the supplements may have led to some memory impairment.

What this shows is how it is important not to overdo any good thing. And that it is critical, though difficult, to determine which beneficial microbes are absent before treating with probiotic supplements on top of a healthy diet. As always, much of the research our microbiomes is directed at teasing out cause and correlation: when can we prevent and heal and when can we merely predict and otherwise act. Do changes in the biome predict disease or prevent disease?

As always, you should test and measure — if you supplement and feel worse, reduce or stop. This requires good record keeping and journaling to track what foods and supplements are working. And, as always, check with your health care provider before making any changes to diet or supplementation.

When do we eat?

I first learned of Intermittent Fasting (IF) from The Secret Life of Fat. In it, Sylvia Tara described how she used IF in her arsenal of tactics to reduce body fat and increase lean muscle mass. This sent me of on a Quest for Fasting.

I found that in addition to longer overnight fasts like Dr. Tara used, practitioners defined a variety of IF routines.

Quest for FastingThere is the long intra-day or overnight fast like Tara’s. These can use early dinner, late breakfast, or both to increase the fasting time.

There are also 5:2 fasts, where you eat for five days and then fast (or calorie restrict) for two days. And a monthly variant, where you calorie restrict for 5 days a month.

Every other day fasts alternate eating and fasting days. One routine employs a 24-hour fast (from the end of dinner on Monday until the start of dinner on Tuesday). Another option is to alternate eating days with 36-hour fasts (from end of dinner on Monday until breakfast Wednesday). Clearly, there is an infinite variety of protocols.

What a difference a day makes

One fasting fact really struck me: the liver stores enough glycogen to supply the body with its glucose needs for at least 24 hours after feeding.

That forced me to think about why we eat when we do.

Empty PlateIt’s natural to think about our food needs on a daily basis. The day is an obvious cycle for us Homo sapiens. Because of this, we think about our Daily energy needs — such as the Daily Minimum Requirements. This leads us to plan and eat in daily “chunks.” Each day we want to meet our calorie and nutrient goals. Then the timer resets overnight and we start over the next day.

But is this daily planning optimal? Worse, is it detrimental?

Let’s imagine, for kicks, a shorter timeframe. What if the way we thought about eating, from our vocabulary to the planning, research studies, and recommendations were hourly instead of daily? We wouldn’t talk about needing 3,200 calories a day, but rather about getting our 200 calories per waking hour. And we’d eat that way. Planning each hourly meal. That’s right, lunch every hour!

Sure, that’s kind of absurd.

But is our daily framework causing a version of this same “eating too frequently” problem? Turns out research supports this conclusion. We simply don’t need to eat every day. I’ve already mentioned that we store enough to supply our glucose needs for twenty-four hours without eating again. But what else justifies spreading out the eating?

What’s the downside of constant eating?

Insulin response is a big factor here. Near constant eating, with a short break to sleep, never lets insulin levels and the important follow-on processes fully reset. Think of those NiCad rechargeable batteries. When you don’t fully drain them all the way before recharging, what happens? Their performance degrades.

EvolutionThere’s an evolution-versus-modern-life dynamic at play here. Between seasons, droughts, fires, monsoons, migrations, and other forces of nature, foods weren’t always available in abundance all year in our pre-history. Three square meals a day (plus some snack bars) was a luxury that just didn’t come that often. Thus, natural selection has left us with systems that are attuned to packing away food (as fat) for our use in the down times.

Think about it. If not eating for a day made us lethargic, light-headed, and dysfunctional, how would we ever have survived as a species? The first drought or winter season would have killed us all.

When we feed all the time, we disrupt the body’s store-and-release process. Our constant eating barely taps our system of stored energy (fat). Like that rechargeable battery, we’re draining a little and topping off every day. And never letting the full system get exercised.

That’s in the best of cases. In the worst case, constantly high insulin levels lead to insulin resistance which cascades into a host of well-known issues like obesity and diabetes.

The modern response to putting on weight, though, has been to limit our daily caloric intake — trying to manipulate the calorie input and output: deficit to lose weight, balanced to maintain weight.

Obesity trends suggest that this doesn’t work. In fact, constant eating at reduced calories triggers different responses than does not eating all. This is the well-known metabolic slow-down and other effects. Fasting is potentially a more evolutionary approach to managing calories and energy supplies with the way our bodies are designed to work, without the side effects of daily calorie restriction.

Better insulin management is just one benefit fasting for longer periods. Studies show improved functions from memory to concentration, to physical agility.

But fasting is sooooo uncomfortable!

With the idea of working towards an every other day routine, I started with a single 24-hour fast. Like most people, I didn’t know what I was in for.  Fear of hunger and discomfort can make fasting hard to start.

Tips to start a fast protocolMy initial 24-hour fast was tough. No denying it. I couldn’t stop thinking about fasting, which of course kept me focused on food — or the lack thereof. I got headaches and a little weak-kneed. But I made it.

Several days later, I fasted again. This time it was much easier. And easier again two days later. Now I’m on an every other day 24-hour fast.

(A side benefit of the 24-hour routine: you don’t skip a dinner, so it’s easy to work into family or social life.)

Hangry, anyone?

Hunger is a big fear for anyone trying to fast. With hunger, though, you quickly realize something: it’s more in your habits than in your gut.

I noticed that much of the hunger cycle is about habit. For what seems like forever, I’ve had a coffee and a snack when I got to the office. Like Pavlov’s dog, getting to my desk was like a bell ringing. My brain told me it was snack time. Once you break these habits and change the stimuli, it is much easier. (See the tips above.)

What about exercise? Not a problem. I’ve been able to do my usual high-intensity-interval-training (HIIT) routine during fast days without a hitch. You have to feel it to believe it: you will not be lethargic or hungry on fast days. And despite the common wisdom, you will not start “burning muscle” when you fast. The body protects the brain first and the muscles second — remember, you need both to find that next meal in the wild. If you do resistance training, you can build muscle on a fasting routine.

So, when do we eat?

The research, and my experience, is starting to show that the answer is: far too often.

Disclaimer: I’m not your doctor. I’m not anyone’s doctor. This material is for information purposes only. Speak with your medical professional before starting any diet or exercise program.

Yo-yo dieting

Is yo-yo dieting killing you?

We all know the story. And the stats. Some 90% or more of weight loss diets fail, and many dieters actually end up heavier. What’s going on?

Are these dieters just lazy? People who’ve never had a weight problem would say so. “Eat less. Move more.” It’s so simple, right?

Short answer: no.

There are a number of factors that help us unpack aphorisms like “eat less, move more” and “calorie in, calorie out.” In short, it’s all relative to your unique factors: food processing genetics, microbiome, age, hormones, gender, viruses, and more.

At some level, yes, within each individual’s body situation, “eat less, move more” may be true.  But how much less and how much more?

The details are too many to discuss here (it would take a book!). So take our word on it for now.

How does this relate to yo-yo dieting?

One key finding is that when you lose fat—like that first 10 pounds that you quickly dropped on your latest diet attempt—your body signaling changes. This is because key signaling hormones are produced by fat itself. The fat goes down, the signaling slows, and profound changes occur.

These changes make you feel hungrier and burn less calories than people never heavier than your new weight. Feeling hungrier, in this case, doesn’t just mean a little bit of tummy growling.

Your brain is going to react differently to food. Seeing food, smelling food, even thinking of food, will all cause stronger emotional reactions than they would have at your starting weight. You will crave more calorie-dense foods. Furthermore, depending on the foods you now eat, you may alter your microbiome. And you’ll feel too strained to exercise as much as you’d like to (because you’re feeling the need to overcome that slower metabolism).

As all these forces align, you fall off the program. The weight goes back up, like that yo-yo.

So you try again on another plan. Same thing. Only the effect is greater. Each time you lose and gain you risk further disturbing your bodies signaling around hunger, digestion, fat storage, insulin sensitivity and a host of factors. On top of it all, your will power, confidence, and mood are taking a beating too.

Would you be better off never trying?

Not knowing what you were getting in to, frankly, yes. The mission was doomed to fail. And the more you yo-yo, the worse your health is getting. It’s literally killing you.

Losing weight and getting rid of fat really strikes a nerve in us modern humans. And we seek silver bullets. Unfortunately, many dieters put more research into choosing a flat-screen TV or a new laptop than they put into choosing a diet plan. (TV manufacturer’s—maybe you should claim to change people’s lives in 10 days.)

To break the yo-yo cycle, you have to put the work in up front and along the way.

First, barring outright snake oil, some people will respond to a particular diet and exercise plan. Keep in mind, though, that your friend who got great results was lucky to have hit on a diet that was aligned to their factors. That doesn’t make the same plan right for your context.

So think about what worked for you and what didn’t in the past. Look for patterns.  Can you eat a moderate amount of carbohydrates—grains and veggies—as long as you don’t overdo the sugar cookies? Or does being in the same room as a banana make you gain weight?

Next, exercise. You’ve heard that building muscle mass will raise metabolism and help you burn fat. True. And you’ve read that high-intensity interval training (HIIT) is a super fat-burner. True again. But, you recall, that when you have done intense exercise, weights or HIIT, it made you so hungry that you overcompensated on the calories. It could be that low-intensity steady state (LISS) workouts will be better for you in the long run.

The point is, you have to research, learn, and experiment to understand what factors are most important for you.

Only then can you get off the yo-yo train.