Glucose, Insulin, & Glucagon in Metabolic Health

Glycemic index is commonly used. In using 10 subjects (presumably on a Standard American diet), it is the measured rate of which foods cause the level of glucose in the blood to rise over a 2-hour period, as compared to the affect of a reference food that is usually pure glucose.

But many question the relevance of the glycemic index. In terms of health, it matters little whether your blood sugar rises over a period of less than or more than 2 hours because the carbs eventually are digested and absorbed. Some argue that an extended and sustained rise of blood sugar is more harmful than a quick boost that goes away quickly. Too much glucose for too long in the blood is toxic — one might say that it’s a heavy load. The body has to deal with the glucose one way or another, either burning it as fuel or storing it as fat.

That is why some prefer glycemic load. It is determined by taking the glycemic index of a food, multiplying it by the net grams of carbohydrate in a standard serving size (e.g., 100 grams), and dividing that by 100. So, it is taking into account the total amount of available carbs in the food. “Glycemic load appears to be a significant factor in dietary programs targeting metabolic syndrome, insulin resistance, and weight loss; studies have shown that sustained spikes in blood sugar and insulin levels may lead to increased diabetes risk[3]” (Glycemic load, Wikipedia). Keep in mind that most Americans have some component of metabolic syndrome: obesity, diabetes, fatty liver, heart disease, etc.

This, of course, ignores satiety. The same serving size of one food won’t be equally satisfying as another food and depending on what it is eaten with as part of a total diet. Neither glycemic index nor glycemic load measures the impact of blood sugar on how much the typical person would eat of a particular food, such as spinach compared to popcorn. Some argue a single serving of potato every day or every other day is healthy for most people, but they don’t take into account that few people would ever only eat one serving of potatoes and eat few if any other carbs for the rest of the day. Even foods with moderate glycemic index and load, if snacked on all day, would keep blood sugars higher than is optimal for long term health. That is the real world impact that gets ignored.

Furthermore, consider the insulin index, which some consider more important than glycemic index or glycemic load. It can be misleading, though, with some foods. Foods high in protein will raise insulin higher than many foods because of gluconeogenesis (protein turned into glucose), but the body only does so to a limited degree and it is an extremely short term spike and then, particularly on a low-carb diet, this is followed by insulin stabilizing at a much lower level. Fatty foods will also kick up insulin levels, although once again not a problem on a low-carb diet. By the way, fat is a complicating factor. Even though fat raises insulin, fatty foods overall have a lower insulin response than non-fatty foods, whether comparing 2% milk and skim milk or a regular cook to a low-fat cookie. This partly has to do with fat moderating the absorption of carbs, but it also has to do with how companies will add sugar to low-fat foods in order to make them taste better.

Anyway, temporary spikes from protein or fat alone are not generally problematic, assuming it’s not part of an otherwise unhealthy diet. Metabolic syndrome is more determined by the sustained increases of insulin, not temporary rises. But the problem with the Standard American diet is that it combines protein and fat with massive amounts of refined carbs, and because many carbs like grains and sugar are addictive this eating pattern is repeated as continuous meals and snacks all day long. There is a reason why, to ignore protein, one can lose weight on both a low-carb diet and a low-fat diet. It’s the combination of the macronutrients in highly processed foods that has such consequences to the metabolic system and, to add to the fire, a high-carb diet is inflammatory as are the industrial seed oils that are used in junk food, fast food, and sadly packaged ‘health foods’.

Still, even these short term spikes can be problematic for diabetics trying to maintain insulin levels. But for non-diabetics, it’s less relevant. As we have glycemic load to show which foods have a sustained rise in blood sugar, we likewise need an insulin load to measure the extended impact of insulin over longer periods. This is particularly important for insulin resistance, as seen in diabetes and what some consider central to metabolic syndrome. It is where the body has to keep raising insulin because the body’s response becomes muted. It’s the constant raising of insulin that causes this muting, not brief occasional spikes.

Also, left out is that blood sugar by itself doesn’t necessarily tell us much. Metabolic syndrome is a disease of insulin, not of blood sugar. But as I said, looking at insulin alone doesn’t necessarily help either. Insulin is a hormone that works with other hormones to maintain the metabolic system. We can only know how an individual is responding, in terms of metabolic health, by measuring the insulin to glucagon ratio. Glucagon can detect diabetes sometimes decades before it otherwise would show up. Any doctor could measure glucagon, although few do.

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Let’s look at a specific food as an example.

Potatoes may seem healthier, but they are still a carbohydrate. Potatoes have a higher glycemic index (high 80s to low 90s) than table sugar (59), although slightly below pure glucose (100). “Sucrose (table sugar) has a GI of 59. It is a disaccharide (two sugar) molecule—it’s made up of one glucose molecule and one fructose molecule. Fructose is processed differently in your body than glucose, and it doesn’t affect your blood sugar as much” (Why Do Potatoes Have a Higher Glycemic Index Than Sugar?). As further comparison, bread has a GI between 40 and 95, depending on the kind.

Likewise, not all potatoes are created equal: “In general, potatoes can range in GI value from 53 to 111, with white potatoes typically showing up lower on the index. Leaving the skin on adds fiber, which can reduce the potato’s effect on glucose. Often, the sweet potato is rated with a GI in the mid-40s.” How they are prepared matters to some degree as well, but that still puts the lowest GI potatoes around the same as table sugar.

The glycemic load, the most important measure, is even worse: “A small study compared the impact 50 grams carbohydrate portion of potatoes versus bread versus pasta had on participant’s blood sugar levels. While clearly none of the foods tested are particularly blood sugar friendly, it’s interesting to note that the potatoes resulted in the most significant rise at the 2 hour mark” (Potatoes and Diabetes: Can You Eat Them?). This also depends on the type of potato with the baked white potato having a high glycemic load of 29 and sweet potatoes around a moderate 19, that is moderate for starchy foods. That is much higher than the glycemic load of bread, from 11 to 16.

The only theoretical advantage to potatoes is resistant starch, but even that is not a net benefit since, “Research has also suggested that increased consumption of potatoes, especially french fries, leads to an increased risk of developing type 2 diabetes.” In case you forgot, type 2 diabetes, like liver disease, are part of metabolic syndrome. So, the basic point is that potatoes don’t contribute to metabolic health and certainly shouldn’t be eaten or at least eaten in extremely small amounts by anyone suffering from any condition of metabolic syndrome.

The author goes on to say that, although it’s true that potatoes have a bit more resistant starch than other high-carb foods, “The problem is that this logic of resistant starch is flawed, similar to the flaws found with the net carb counting method. First, the amount of resistant starch found in a medium potato is about 9 grams, which still leaves around 28 grams of fully digestible carbohydrate available to spike your blood sugar. Resistant starch in and of itself offers health benefits such as improved glycemic control, but in order to eat enough resistant starch (from potatoes, rice, and unripened bananas) you would end up eating an outrageous amount of carbohydrate.”

Let us touch upon the insulin index. Like refined grains, potatoes have a high insulin response. This would vary by kind of potato and preparation method, I’m sure. But interestingly, another factor alters the insulin effect. I mentioned fat above in how it moderates carbohydrate absorption. This is demonstrated by comparing two products that only differ by fat amounts (Forget Calorie Counting; It’s the Insulin Index, Stupid).

A normal potato chips have an insulin index of 45 whereas it’s 51 for 40% reduced-fat potato chips. I don’t know exactly what that means. A low-fat diet can be used to lose weight, but that is a separate issue from the insulin index. Both obesity and high insulin responses contribute to insulin resistance. I guess you could solve this problem by cutting out the potatoes along with most other starchy carbs and then you have nothing to worry about. Potatoes are high insulin response for potatoes, though a bit lower with fat, is still on the higher end of the scale.

The next bit of info comes from an article that seems balanced in the mainstream sense with no particular alternative slant, such as low-carb or vegan. Interestingly, it comes from the Food Revolution Network with their show co-hosted by John Robbins who “was groomed to be the heir to the Baskin-Robbins empire” who left the family business because “He simply didn’t want to devote his life to selling ice cream after realizing it makes people unhealthy.” So, the only bias might be against commercial ice cream.

The author states that, “Potatoes can be a healthy choice for most people…” But… there is always a but: “but three groups might want to minimize their consumption (particularly of white potatoes): pre-diabetics, diabetics, and people who are overweight” (Are Potatoes Healthy? The Surprising Truth About This Controversial Vegetable), and presumably any other condition involving metabolic syndrome/derangement, such as fatty liver. That means anyone who isn’t metabolically healthy should avoid or minimize potatoes in their diet and, as we know, most Americans aren’t metabolically healthy.

On the other hand, “But, in a published in the Journal of the American College of Nutrition in 2014, researchers found that when people followed healthy recipes, they lost weight even while eating five to seven servings of potatoes per week.” So, it’s possible that someone by eating generally healthy, in removing all the common problematic foods, might be able to regain enough metabolic health to eat some starchy foods like potatoes. Still, even then, a serving of potatoes is fairly small. Few people eating potatoes are likely to limit themselves to a single serving, not to mention all the other starchy carbs they are also likely to eat throughout the day.

It goes back to the challenge of modern society. In a few traditional societies, they did eat relatively more carbs as a percentage of their diet. But that is in the context of their diet in general being typically limited and often to an extreme degree with small portions and caloric restriction. That is the key point that goes unspoken. If one is to eat a higher-carb diet or even merely a moderate-carb diet, in any case not low-carb, one should all the more closely follow a traditional diet and lifestyle: pasture-raised animal foods, regular cardio exercise and strength training, etc.

Still, a higher carb diet was rare until the modern era. The highest end of the carbohydrate range of hunter-gather diets at 40% of calories, I like to point out, is what some Western researchers define as part of a ‘low-carb’ diet (Cordain et al, Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets). So, even at the highest amounts for hunter-gatherers, they are still getting most of their energy and nutrients from animal foods. And guess what? Obesity, diabetes, and heart disease is rare among most of these populations — that is as long as they remain on their traditional diets.

Sweeteners Can Mess You Up!

Sugar, in large doses, is a harmful substance. Many people have warned against sugar going back to the 1800s. The strongest case was made against it by the physiologist, nutritionist, and professor John Yudkin back in 1972 with his book Pure, White and Deadly. For speaking the truth, his reputation was destroyed by Ancel Keys. But more recently, the science journalist Gary Taubes brought the topic back to public attention, in his own book The Case Against Sugar.

Yudkin has been vindicated, as Keys original research that blamed saturated fat for heart disease has since been re-analyzed and shown that sugar is the stronger correlation. We also now understand the science of why that is the true. But it isn’t only about sugar. The sweet taste, whether from sugar or non-nutritive sweeteners, still causes many of the same problems. All sweeteners affect insulin, gut microbiome, cell functioning, neurocognition, mood, and much else. For example, consumption of both sugar and aspartame is associated with depression, at least in one study that was a randomized controlled trial (G. N. Lindseth, Neurobehavioral Effects of Aspartame Consumption).

They do alter serotonin levels, if not dopamine in all cases — some sweeteners affect dopamine and some don’t. This is observable in how people addicted to sugar so easily shift to non-sugar sweeteners and then act in the same addicted way, finding it hard to imagine giving them up. One way or another, addictive pathways seem to be elicited. The brain isn’t fooled and so the body still will hunger for the sugar it thinks it is getting from the sweet taste.

Exchanging one addictive substance, sugar, for another, non-sugar sweetener, is not a benefit. The problem is the addiction itself. A diet high in carbs and sugars is addictive. Throwing in some other kinds of sweeteners doesn’t change this. The best option is to break the addictive cycle entirely by going low-carb or, better yet, ketogenic. And there is no evidence that artificial sweeteners can be used with a ketogenic diet, since they might knock the body out of ketosis in the way sugar does. To be certain, just eliminate all sweeteners and so kill the problem at its root.

On the other hand, that can be easier said than done. I know sugar addiction, as in I was a sugar fiend from childhood to my thirties. And I did for years increase my use of other sweeteners, in an attempt to break free from the hold sugar had over my brain and mood. This wasn’t a particularly successful strategy. And my health was not improved, as the non-sugar sweeteners maintained my high-carb cravings.

I simply had to cut them out strictly. This simple truth is reinforced every time I slowly increase sweeteners in my diet and the cravings creep back in. I just don’t feel good with them. The lesson has been fully learned at this point.

It was amazing what a difference it made once my sweet tooth went away. Only then did my physical health improve and my psychological health soon followed. I can’t emphasize this enough. Carbs, sugars, and other sweeteners will seriously mess you up over time. You might not notice it for decades, but it all catches up with you. The damage is being done, even if you don’t notice it slowly accumulating. And realize the consequences won’t be limited to sickliness of obesity, diabetes, and heart disease, as neurocognitive and mental health can also decline (e.g., Alzheimer’s is now called type 3 diabetes by some).

An occasional sweet at a birthday party or holiday gathering is one thing. Maybe you can have that and immediately go back on a healthy low-carb diet. Maybe or maybe not. If you were ever a sugar addict, as most Americans are, you are tempting fate. It’s like a recovering alcoholic taking that first sip of whiskey, vodka, or beer; like the recovering druggie getting that first shot of heroin or puff of the crack pipe.

Sugar is a drug, as research shows, that elicits the same reward pathway in the brain as other drugs and all sweeteners can elicit the same or similar pathways. You’ll hunger for more. And even if other sweeteners don’t have all of the problems of sugar, they still have plenty of potential problems that could do serious harm to your health over time.

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Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response
by Qiao-Ping Wang et al

The truth about artificial sweeteners – Are they good for diabetics?
by Vikas Purohit and Sundeep Mishra

Consuming low-calorie sweeteners may predispose overweight individuals to diabetes
by Jenni Glenn Gingery and Colleen Williams

Not So Sweet: Metabolic Problems Caused by Artificial Sweeteners
by Serena Cho

Artificial Sweeteners Impact Metabolic Health Even on Cellular Level
by Kristen Monaco

Artificial Sweeteners Could be Sabotaging Your Microbiome, Says Study
by Amel Ahmed

Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials
by Francisco Javier Ruiz-Ojeda et al

Sugar Substitutes or Sugar: What’s Better for Diabetes?
by Kathleen Doheny

Artificial sweeteners linked to diabetes and obesity
by James Brown and Alex Conner

Artificial Sweeteners: Agents of Insulin Resistance, Obesity and Disease
by Loren Cordain

The Unbiased Truth About Artificial Sweeteners
by Chris Kresser

How Artificial Sweeteners Wreak Havoc on Your Gut
by Chris Kresser

Artificial Sweeteners Can Lead to Diabetes In Overweight People
by Gundry MD Team

Artificial Sweeteners Could Be Ruining Your Gut Health
by Gundry MD Team

Are Artificial Sweeteners Safe for the Brain and Gut
by Siim Land

Artificial Sweeteners Don’t Fool Your Brain
by Joseph Mercola

Tricking Taste Buds but Not the Brain: Artificial Sweeteners Change Brain’s Pleasure Response to Sweet
by Caitlin Kirkwood

Artificial Sweeteners: Why You Should Completely Avoid Them to Stay Healthy
by Elizabeth Lyden

Aspartame: 11 Dangers of This All-Too-Common Food Additive
by Rebekah Edwards

Aspartame Side Effects: Recent Research Confirms Reasons for Concern
by University Health News Staff

The Effects of Aspartame on Fibromyalgia and Chronic Fatigue Syndrome
by Adrienne Dellwo

Are Artificial Sweeteners Damaging Your Blood Vessels?
by Michelle Schoffro Cook

Direct and indirect cellular effects of aspartame on the brain
by P. Humphries, E. Pretorius, and H. Naudé

Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain.
by R. P. Sharma and R. A. Coulombe Jr.

Neurophysiological symptoms and aspartame: What is the connection?
by Arbind Kumar Choudhary and Yeong Yeh Lee

The debate over neurotransmitter interaction in aspartame usage
by Arbind Kumar Choudhary and Yeong Yeh Lee

The Connection between Aspartame (Artificial Sweetener) and Panic Attacks, Depression, Bipolar Disorder, Memory Problems, and Other Mental Symptoms
by Betty Martini

Side-Effects of Aspartame on the Brain
by Michael Greger

Migraine Triggers: Artificial Sweeteners
by Jeremy Orozco

Intense Sweetness Surpasses Cocaine Reward
by Magalie Lenoir , Fuschia Serre , Lauriane Cantin, and Serge H. Ahmed

Diet Soft Drinks Linked to Depression
by Naveed Saleh

Why is Diet Soda Addictive?
by Edward Group

Neurobiology of Addiction
by George F. Koob, Michel Le Moal
pp. 448

Accumulating evidence also suggests that dopamine is not required for nondrug reward. In a study in which dopamine release in the nucleus accumbens core and shell was measured with precise voltammetric techniques during self-stimulation, it was shown that if dopamine activation is a necessary condition for brain stimulation reward, evoked dopamine release is actually not observed during brain stimulation reward and is even diminished (Garris et al, 1999). Also, mice completely lacking tyrosine hydroxylase, such that they cannot make dopamine, demonstrated the ability to learn to consume sweet solutions and showed a preference for sucrose and saccharin. Dopamine was not required for animals to find sweet tastes of sucrose or saccharin rewarding (Cannon and Palmiter, 2003; Cannon and Bseikri, 2004).

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I wrote this post as a response to a video, Keto & Beverages, by the LCHF advocate Dr. Westman.

Below is an amusing and irritating (and, sadly, all too common) dialogue or miscommunication I had with Dr. Eric Westman or someone writing on his behalf at his Youtube channel, Adapt Your Life. The most frustrating part is that I’m mostly in agreement with Dr. Westman, as I too adhere to LCHF. For that reason, I don’t want to be harshly critical nor do I want to be polarized into a stronger position than I actually support, but I must admit that my emotional response was a bit negative.

To stand back from the disagreement, I don’t even have a strong opinion on what others do in terms of sweeteners. I don’t recommend sweeteners, sugar or otherwise, based on personal experience. But if artificial sweeteners help some people to transition to a healthier diet (or if they believe this to be true, and I won’t dismiss the placebo effect), then more power to them. Anyway, here is the interaction that rubbed me the wrong way:

Me: “Wasn’t there a recent study that showed even artificial sweeteners can lead to diabetes? The body still responds to the sweet taste as if it were sugar and over time messes with insulin sensitivity.”

Other person: “Hi Ben Steele, I’m not sure we have seen this study.”

Me: “I decided to write a post about it. I found the info I was looking for. At the end of the post, I share links to it and other info about the problems with non-sugar sweeteners.

“As a recovering sugar addict who followed that up with addiction to other sweeteners, I personally would recommend against such substances. But each individual has to decide for themselves.”

[I then linked to this post.]

Other person: “Hi Ben Steele, we opened a couple and didn’t find an actual “study”. Just peoples opinion and thoughts. We would be interested to read a study, preferably a RCT as this is the gold standard of studies. Thanks for this 😊”

Me: “Multiple links were to “studies”. The first two links are papers on studies, the third is the press release of a study, the fourth is a Yale report about a Yale study, five more links further down are papers on studies, and the last is a quote from an academic book from a university press. So, about a third of them linked to studies and academic material. As for all the rest, they directly reference and discuss numerous other studies.

“If you are interested to read a study, then do so. But if not, then don’t. I can’t force you to read anything.”

To further respond, I’m not sure how much of the research is randomized controlled trial. But after doing a casual research that as easily could’ve done by Dr. Westman or his staff, I found info on RCT research. I noticed it briefly mentioned in a few links above, but I didn’t check all the links. I did find RCTs on the topic elsewhere in doing a web search.

I still find it irritating, though. It feels hypocritical. Dr. Westman or his representative was acting with condescension, intentional or not.

Why is this person demanding RCTs of me when they don’t hold themselves to this same standard? Dr. Westman offered no RCTs to back up his recommendations. And these artificial sweeteners were approved by the FDA without any RCTs proving their safety. So, why is it that critics have to prove they are unsafe? Why would we allow invented chemicals to be put on the market and then have doctors recommend them to patients without knowing their long-term safety or side effects?

Just to prove my point, I will share some RCT evidence (see below). And to be fair, I will admit that the results are mixed and, one might argue, inconclusive — consider aspartame that has been researched more fully (see: Travis Saunders, Aspartame: Cause of or Solution to Obesity?; and Michael Joseph, Is Aspartame Safe Or Is It Bad For You?). But based on a familiarity with the available research, without more and better research, no sane and reasonable person would give artificial sweeteners a clean bill of health and proclaim them safe for general mass consumption, especially on a regular basis as a preferred flavoring. Whether or not artificial sweeteners cause weight gain, those might be the least of our worries, in terms of potential side effects seen in some of the studies. Some precautionary principle is in order.

Still, yes, it is hard to state a strong opinion about present evidence, beyond a note of caution. But every individual is free to dismiss such caution and use artificial sweeteners anyway. They might or might not be helpful in losing weight, even if used long enough might lead to detrimental outcomes in other areas of health. Maybe that risk seems worthwhile, assuming short-term weight loss is all that concerns you, and assuming that short-term use won’t lead to long-term use and won’t sabotage a long-term healthy diet. Individuals should make a decision with eyes wide open with the knowledge of potential risks that could be quite serious.

I understand. There are also potential benefits. For those addicted to sugar, they are dealing with a highly destructive substance. Artificial sweeteners may seem like the only choice. And who am I to judge. That is what I did. While transitioning off sugar, I spent a number of years consuming my fair share of laboratory-invented sweeteners. It did get me off sugar, but then all that happened was I was addicted to these other sweeteners. It maintained my sweet tooth and so encouraged me to continue eating a diet high in carbs and sugar. There was no obvious benefit. It did eventually lead me to give up all sweeteners. I just don’t know that the artificial sweeteners were more of a help or a hindrance in that process.

Whatever your decision, know that these substances aren’t without risks. It is dietary Russian roulette. Maybe there will be no serious harm and maybe there will. We shall all find out decades from now when the children and young adults raised on these chemicals reach older age. Here is my perspective. Why take any risk at all when it is completely unnecessary? We already know how to stop sugar cravings in their tracks. With a ketogenic diet, you won’t need to exchange addiction to sugar with an addiction to artificial sweeteners. It’s the simplest solution and, for such people, the only solution with a guaranteed net positive health outcome.

As a quick note, I’d point out a few things about the research. First, all sweeteners affect the body and so aren’t neutral substances, but it is unknown if the effects are a net benefit or net loss. Also, different sweeteners have different effects and the reason for this is not entirely understood. There are still other concerns.

The worst effects in animal studies were seen with high doses, which makes one wonder what is the effect of artificial sweeteners combined with the effect numerous other chemicals, additives, toxins, and pollutants, along with other physiological and environmental stressors that most people are exposed to, as the interaction of multiple factors is an area that mostly remains unexplored and, more importantly, rarely controlled for. And as far as I know, no study has ever been done with various sweeteners in relation to low-carb, zero-carb, and ketogenic diets; whereas most of the studies that have been done are using subjects on the severely unhealthy standard American diet, and so maybe for those people an artificial sweetener is better than the alternative of a high-sugar diet.

Basically, we are in a state of far greater ignorance than knowledge. It’s anyone’s guess. As always, you are taking your life into your own hands. Whatever a journalist, doctor, or health expert may say, it is in the end your life that is at stake, not theirs.

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Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings
by Qing Yang

[C]onsensus from interventional studies suggests that artificial sweeteners do not help reduce weight when used alone [2,25]. BMI did not decrease after 25 weeks of substituting diet beverages for sugar-sweetened beverages in 103 adolescents in a randomized controlled trial, except among the heaviest participants [26]. Adouble blind study subjected 55 overweight youth to 13 weeks of a 1,000 Kcal diet accompanied by daily capsules of aspartame or lactose placebo. Both groups lost weight, and the difference was not significant. Weight loss was attributed to caloric restriction [27]. Similar results were reported for a 12-week, 1,500 Kcal program using either regular or diet soda [28]. Interestingly, when sugar was covertly switched to aspartame in a metabolic ward, a 25 percent immediate reduction in energy intake was achieved [29]. Conversely, knowingly ingesting aspartame was associated with increased overall energy intake, suggesting overcompensation for the expected caloric reduction [30]. Vigilant
monitoring, caloric restriction, and exercise were likely involved in the weight loss seen in multidisciplinary programs that included artificial sweeteners [31,32].

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies
by Meghan B. Azad, Ahmed M. Abou-Setta, Bhupendrasinh F. Chauhan, Rasheda Rabbani, Justin Lys, Leslie Copstein, Amrinder Mann, Maya M. Jeyaraman, Ashleigh E. Reid, Michelle Fiander, Dylan S. MacKay, Jon McGavock, Brandy Wicklow, and Ryan Zarychanski

Evidence from small RCTs with short follow-up (median 6 mo) suggests that consumption of nonnutritive sweeteners is not consistently associated with decreases in body weight, BMI or waist circumference. However, in larger prospective cohort studies with longer follow-up periods (median 10 yr), intake of nonnutritive sweeteners is significantly associated with modest long-term increases in each of these measures. Cohort studies further suggest that consumption of nonnutritive sweeteners is associated with higher risks of obesity, hypertension, metabolic syndrome, type 2 diabetes, stroke and cardiovascular disease events; however, publication bias was indicated for type 2 diabetes, and there are no data available from RCTs to confirm these observations.

Previous reviews12,65 concluded that, although data from RCTs support weight-loss effects from sustained nonnutritive sweetener interventions, observational studies provide inconsistent results. Building on these findings, we included new studies14–24 and found that consumption of nonnutritive sweeteners was not generally associated with weight loss among participants in RCTs, except in long-term (≥ 12 mo) trials with industry sponsorship. In addition, we found that consumption of nonnutritive sweeteners was associated with modest long-term weight gain in observational studies. Our results also extend previous meta-analyses that showed higher risks of type 2 diabetes32,33 and hypertension66 with regular consumption of nonnutritive sweeteners.

Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial
by Alonso Romo-Romo, Carlos A. Aguilar-Salinas, Griselda X. Brito-Córdova, Rita A. Gómez-Díaz, and Paloma Almeda-Valdes

We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). […]

Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence.

Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations.

Neurobehavioral Effects of Aspartame Consumption
by Glenda N. Lindseth, Sonya E. Coolahan, Thomas V. Petros, and Paul D. Lindseth

Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40–50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health.

Artificial Sweeteners: A Systematic Review and Primer for Gastroenterologists
by Marisa Spencer, Amit Gupta, Lauren Van Dam, Carol Shannon, Stacy Menees, and William D Chey

Artificial sweeteners (AS) are ubiquitous in food and beverage products, yet little is known about their effects on the gastrointestinal (GI) tract, and whether they play a role in the development of GI symptoms, especially in patients with irritable bowel syndrome. Utilizing the PubMed and Embase databases, we conducted a search for articles on individual AS and each of these terms: fermentation, absorption, and GI tract. Standard protocols for a systematic review were followed. At the end of our search, we found a total of 617 eligible papers, 26 of which were included. Overall, there is limited medical literature available on this topic. The 2 main areas on which there is data to suggest that AS affect the GI tract include motility and the gut microbiome, though human data is lacking, and most of the currently available data is derived from in vivo studies. The effect on motility is mainly indirect via increased incretin secretion, though the clinical relevance of this finding is unknown as the downstream effect on motility was not studied. The specific effects of AS on the microbiome have been conflicting and the available studies have been heterogeneous in terms of the population studied and both the AS and doses evaluated. Further research is needed to assess whether AS could be a potential cause of GI symptoms. This is especially pertinent in patients with irritable bowel syndrome, a population in whom dietary interventions are routinely utilized as a management strategy.

Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies
by Ingrid Toews, Szimonetta Lohner, Daniela Küllenberg de Gaudry, Harriet Sommer, Joerg J Meerpohl

In one randomised controlled trial,85 total cholesterol concentration decreased strongly in sucrose groups but increased in the aspartame group (mean difference 0.44 mmol/L, 95% confidence interval 0.33 to 0.56; n=45). […]

In one crossover non-randomised controlled trial,83 researchers found a significantly higher increase in blood glucose in children of preschool age receiving aspartame compared with sucrose (mean difference 0.24 mmol/L, 95% confidence interval 0.09 to 0.39; n=25), a significantly higher increase in blood glucose in children of school age receiving saccharin compared with sucrose (0.65 mmol/L, 0.44 to 0.86; n=23), and a significantly lower increase in blood glucose in children of preschool age receiving aspartame compared with saccharin (−0.75 mmol/L, −0.95 to −0.64; n=23, very low certainty of evidence). In overweight children involved in active weight loss, blood glucose decreased less strongly in those receiving NSSs compared with those not receiving NSSs (0.3 mmol/L, 0.2 to 0.4; n=49, very low certainty of evidence).

Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants
by A. Mishra, K. Ahmed, S. Froghi, and P. Dasgupta

The statistical value of this review is limited by the heterogeneity and observational designs of the included studies. Although there is limited evidence to
suggest that heavy consumption may increase the risk of certain cancers, overall
the data presented are inconclusive as to any relationship between artificial sweeteners and cancer.

Evidence suggesting artificial sweeteners may be harmful should give us pause
by Leslie Beck

The study, a randomized controlled trial, investigated the effect of daily sucralose consumption on insulin sensitivity in 66 healthy, normal-weight adults who didn’t regularly use artificial sweeteners. […]

This finding is provocative because it suggests that regular consumption of sucralose can lead to insulin resistance in healthy, normal-weight people.

Sucralose may affect blood sugar control by activating sweet taste receptors in the gut, triggering the release of insulin. Artificial sweeteners are also thought to disrupt the balance of good gut bacteria in a direction that can lead to insulin resistance and weight gain.

Did America Get Fat by Drinking Diet Soda?
by Daniel Engber

Perhaps more to the point, researchers have tested the effects of diet soda on people trying to lose weight, and gotten positive results. A randomized, controlled trial published in May compared the efficacy of artificially sweetened beverages and water in a 12-week weight-loss program. Both treatment groups ended up with smaller waists, and the people taking diet drinks appeared to lose more weight. That study’s lead authors are consultants for Coca-Cola, so perhaps we shouldn’t take this as the final word. But another randomized trial from 2012, this one funded by a bottled-water company, came to a similar conclusion. When overweight and obese adults switched to diet beverages or water for a six-month stretch, both groups shed 1 inch of girth, on average, and 5 pounds.

Health outcomes of non-nutritive sweeteners: analysis of the research landscape
Szimonetta Lohner, Ingrid Toews, and Joerg J. Meerpoh

Finally, we included 372 studies in our scoping review, comprising 15 systematic reviews, 155 randomized controlled trials (RCTs), 23 non-randomized controlled trials, 57 cohort studies, 52 case-control studies, 28 cross sectional studies and 42 case series/case reports.

In healthy subjects, appetite and short term food intake, risk of cancer, risk of diabetes, risk of dental caries, weight gain and risk of obesity are the most investigated health outcomes. Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes. Numerous health outcomes including headaches, depression, behavioral and cognitive effects, neurological effects, risk of preterm delivery, cardiovascular effects or risk of chronic kidney disease were investigated in fewer studies and further research is needed. In subjects with diabetes and hypertension, the evidence regarding health outcomes of NNS use is also inconsistent.

Early-Life Exposure to Non-Nutritive Sweeteners and the Developmental Origins of Childhood Obesity: Global Evidence from Human and Rodent Studies
by Alyssa J. Archibald, Vernon W. Dolinsky, and Meghan B. Azad

Non-nutritive sweeteners (NNS) are increasingly consumed by children and pregnant women around the world, yet their long-term health impact is unclear. Here, we review an emerging body of evidence suggesting that early-life exposure to NNS may adversely affect body composition and cardio-metabolic health. Some observational studies suggest that children consuming NNS are at increased risk for obesity-related outcomes; however, others find no association or provide evidence of confounding. Fewer studies have examined prenatal NNS exposure, with mixed results from different analytical approaches. There is a paucity of RCTs evaluating NNS in children, yielding inconsistent results that can be difficult to interpret due to study design limitations (e.g., choice of comparator, multifaceted interventions). The majority of this research has been conducted in high-income countries. Some rodent studies demonstrate adverse metabolic effects from NNS, but most have used extreme doses that are not relevant to humans, and few have distinguished prenatal from postnatal exposure. Most studies focus on synthetic NNS in beverages, with few examining plant-derived NNS or NNS in foods. Overall, there is limited and inconsistent evidence regarding the impact of early-life NNS exposure on the developmental programming of obesity and cardio-metabolic health. Further research and mechanistic studies are needed to elucidate these effects and inform dietary recommendations for expectant mothers and children worldwide.

Noncaloric Sweeteners in Children: A Controversial Theme
by Samuel Durán Agüero, Lissé Angarita Dávila, Ma. Cristina Escobar Contreras, Diana Rojas Gómez, and Jorge de Assis Costa

On the other hand, three transversal studies, including 385 and 3311 children, showed positive association between the intakes of NCS and BMI [53]. Similar results were obtained with pregnant woman who ingested NCS, showing more probability of having babies with increased risk for later obesity or overweight. However, the limitation of the studies is that these were of observational type, and the findings do not necessarily imply a significant correlation between the intake of artificial sweeteners and weight gain [54, 55]. In a meta-analysis of intake of NCS that included 11.774 citations, 7 trials, 1003 participants, and 30 cohort studies (adults and adolescents) it was concluded that there is not enough evidence from randomized controlled trials to demonstrate the positive effect of NCS on controlling body weight. Findings of observational studies suggest that the continuous ingestion of NCS could be associated with BMI and cardiometabolic risk increase [56].

Diet Soda May Alter Our Gut Microbes And Raise The Risk Of Diabetes
by Allison Aubrey

While the findings are preliminary, the paper could begin to explain why studies of diet soda point in opposite directions.

“All of us have a microbiome” made up of trillions of organisms. “[It’s] extremely complex. Everybody’s microbiome is a little different,” Blaser says.

And the ways our microbiomes respond to what we eat can vary, too.

In the study, the Israeli researchers find that as mice and people started consuming artificial sweeteners, some types of bacteria got pushed out, and other types of bacteria began to proliferate.

It could be that for some people who responded negatively to the artificial sweetener, the bacteria that got crowded out were helping to keep glucose in check.

How it’s happening isn’t clear, and Blaser says a lot more research is needed.

“So that’s the next step,” Blaser says. “Firstly, for [researchers] to confirm this, to see if it’s really true.” And the next challenge is to understand the mechanism. “How does the change in the microbial composition — how is it causing this?”

Lots of researchers agree they’d like to see a large-scale study.

“It’s much too early, on the basis of this one study, [to conclude that] artificial sweeteners have negative impacts on humans’ [risk for diabetes],” says James Hill, director of the Center for Human Nutrition at the University of Colorado.

He points to a randomized controlled trial published in 2011 that found artificial sweeteners helped to limit the rise in blood sugar in a group of slightly overweight people, compared with sugar.

Hill also points to a study of people on the National Weight Control Registry that found successful long-term dieters tend to consume artificially sweetened foods and beverages at a higher rate compared with the general population.

So expect the debate over diet sodas to continue — and also anticipate hearing more about the role of our microbiomes.

Study links artificial sweeteners and weight gain
by Staff

Azad said what her team was most struck by was the lack of good, rigorous studies on artificial sweeteners.

“Surprisingly, given how common these products are, not many studies have looked at the long-term impact of their consumption,” Azad told CTV News Channel from Lisbon, Portugal.

She noted that only seven of the 37 studies they reviewed were randomized controlled trials (RCTs), and all were relatively short, following participants for a median period of only six months.

The other 30 studies were longer and followed the participants for an average of 10 years, but they were observational studies – a form of research that is not as precise as a controlled trial.

“A lot of the studies we found were observational, meaning they could show a link but they can’t prove a cause-and-effect relationship,” she said.

Among the seven RCT’s, regular consumption of sweeteners had no significant effect on weight loss. From the other studies, the team found that regular use of sweeteners was associated with an increased risk of type 2 diabetes and high blood pressure, and modest increases in weight and waist circumferences.

“What we found was that at the end of the day, from all of this research, there really wasn’t firm evidence of a long-term benefit of artificial sweeteners. And there was some evidence of long-term harm from long-term consumption,” Azad said.

As for why artificial sweeteners seem to be linked to weight gain, not weight loss, Azad says no one knows for sure but there are lots of theories.

One theory is that the sweeteners somehow disrupt healthy gut bacteria. Another theory is that the sweeteners confuse our metabolisms, causing them to overreact to sugary tastes.

It could be that those who regularly use artificial sweeteners over-compensate for the missed calories from sugar, or they could have otherwise unhealthy diets in conjunction with sweetener use.

Azad would like to see a lot more research on the long-term use of sweeteners, in particular studies that could compare the different sweeteners, to see if one is any better than another.

In the meantime, for those trying to cut down on their sugar consumption, Azad says it’s important not to switch from one harmful food item to another.

“I think the takeaway for Canadians at this point is to maybe think twice about whether you really want to be consuming these artificial sweeteners, particularly on an everyday basis,” Azad said, “because really we don’t have evidence to say for sure whether these are truly harmless alternatives to sugar.”

Dr. Eric Berg on Insulin Resistance

Let me do a simple post by sharing a short video. Dr. Eric Berg has a talent for summarizing scientific explanations in a minimal amount of time. Watching it will require less than 10 minutes of your life. And after watching it, you’ll understand why insulin is so important, why insulin resistance is so problematic, and why a low-carb diet is so necessary. It’s simple and to the point.