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Brain Activity & Connectivity Changes: Response to Natural Sugar Replacements & Artificial Sweeteners – Nutritional Neuroscience

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ARTICLE: Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners

AUTHORS:  van Opstal AM, Hafkemeijer A, van den Berg-Huysmans, Hoeksma M, Mulder TP, Pijl H, Rombouts SARB, van der Grond J

SOURCE: Nutritional Neuroscience, Published online July 2019 https://doi.org/10.1080/1028415X.2019.1639306

SUMMARY BY:  Robyn Flipse, MS, MA, RDN

INTRODUCTION

Maintaining energy balance involves many parts of the brain that regulate the homeostatic processes related to food ingestion and the hedonic responses that signal satiety and control feeding behavior. An understanding of how different sweeteners might affect these brain functions and sweet taste cravings is of critical importance given the rising consumption of sugars and non-nutritive sweeteners over the past fifty years and the tandem increase in the incidence of obesity.

This study was designed to investigate the effects of different nutritive and non-nutritive sweeteners on whole brain neuronal activity and network connectivity when the sweeteners were ingested in shakes containing protein and fat. The hypothesis was that the nutritive, naturally-occurring sugars would elicit a response from the brain not seen after consuming the non-nutritive sweeteners due to their lack of caloric content.

BACKGROUND

The brain responds readily to the ingestion of glucose because of its quick absorption, with the glucose sensing neurons in the hypothalamus showing a homeostatic satiety response almost immediately after ingestion. Glucose ingestion also has effects on neuronal activity and functional connectivity throughout the brain areas involved in reward and feeding behavior, while circulating blood glucose levels influence the central nervous system regulation of glucose homeostasis.

Other mono- and disaccharides and low or non-nutritive sweeteners follow different metabolic pathways upon ingestion and have different effects on energy intake and regulation. Earlier findings reported by these researchers indicate that the homeostatic and hedonic responses, as measured by BOLD signal changes in the hypothalamus and ventral tegmental area (VTA), are driven by sweet taste coupled with caloric content. They also found sweet taste without caloric content, as found in non-nutritive sweeteners, did not seem to elicit a lasting response from these brain areas.

Based on these findings, this study used measurements of local BOLD changes of neuronal activity to analyze the immediate effects of nutrient ingestion on very specific areas of the brain and various functional networks involved in feeding behavior and energy balance. The networks they focused on were the default mode reflecting a baseline state of the brain that has been shown to be altered in obesity, the salience network involved in feeding behavior and reward, and the executive control network involved in decision making and impulse control.

Another method used to determine functional brain connectivity was the eigenvector centrality mapping (ECM). It can determine the level and quality of connectivity on a voxel-wise level rather than on a network level and has been shown to be correlated with states of hunger and satiety.

STUDY DESIGN

Subjects were recruited through local advertising and included 20 non-smoking Caucasian men, aged 18-25 years. All had a BMI between 20-23 kg/m2 with no recent weight changes, height between 170-190cm and weight above 70kg. Exclusion criteria included no history of disturbances in glucose metabolism, significant chronic disease or psychiatric disease.

The entire study was performed in a double-blinded, 4-times crossover design. Subjects underwent a resting state functional MRI (rsfMRI) before and after ingesting each of the four different shakes offered in a randomized sequence, with a washout period of at least one week between the four study visits.  Subjective feelings of hunger, fullness, wanting a meal at baseline, and wanting to continue ingestion after first tasting and full ingestion of the shakes were indicated on a Visual Analogue Scale (VAS) consisting of a 10cm line with “not at all” and “extremely” as the anchors.

The shakes were sweetened with either the natural sugars glucose or fructose, the low-nutritive but naturally-occurring sugar allulose, or the non-nutritive sweetener sucralose. All preparations were matched to glucose for sweetness and contained equal amounts of water, sodium caseinate (.33g protein), coconut oil (5g fat), guar, and cocoa powder for flavoring. The test dosage was 165ml and had the sweetness, consistency and macronutrients similar to that found in commercially available milkshakes from fast food chains.

RESULTS

Data from this study confirm previous findings that glucose is a critical signal regulating response to food cues. Brain activity was diminished after ingesting the glucose shakes in the regions that were actively seeking reward or energy when in a fasted state.  Additionally, a small decrease in voxel based connectivity was seen after glucose ingestion in the area containing the hypothalamus and VTA, which are involved in homeostatic and hedonic regulation of energy intake, and glucose was the only condition that led to a significant increase in connectivity in the salience network involved in feeding behavior, determining reward, emotional arousal and decision making.

Ingestion of the fructose sweetened shake had various effects on functional brain response, but the lack of a decrease in activity in the hypothalamus, VTA and other midbrain areas suggests fructose might not have a homeostatic and satiation effect which could affect feeding behavior. This may be due to the fact the effects of fructose on brain connectivity are delayed since it is metabolized in the liver. The low and non-nutritive sweeteners allulose and sucralose had little to no effect on the functional brain responses measured.

These findings indicate shakes with little energy from carbohydrates had no immediate effect on the activity of the brain areas involved in feeding behavior, even though the fat and protein in the shakes did deliver a significant amount of total energy. It further suggests that sweet taste without the presence of carbohydrates does not lead to the activity changes measured with fMRI often associated with satiety. This is consistent with other research that shows sweet taste without energy content does not lead to a lasting decrease in hypothalamic activity.

CONCLUSION

These findings show that even in mixed meals, different types of sweeteners can elicit different brain responses that might, in turn, affect feeding behavior. Nutritive sweeteners elicit a reaction from the brain that could have effects on feeding behavior and reward. Because non-nutritive sweeteners elicited little to no effect, they might not have effects on feeding behavior, neither positive nor negative. Therefore, with regard to regulating energy balance and feeding behavior, non-nutritive sweeteners could be used as neutral replacements for nutritive sugars.

Robyn Flipse, MS, MA, RDN is a registered dietitian, cultural anthropologist and scientific advisor to the Calorie Control Council, whose 30+ year career includes maintaining a busy nutrition counseling practice, teaching food and nutrition courses at the university level, and authoring 2 popular diet books and numerous articles and blogs on health and fitness. Her ability to make sense out of confusing and sometimes controversial nutrition news has made her a frequent guest on major media outlets, including CNBC, FOX News and USA Today. Her passion is communicating practical nutrition information that empowers people to make the best food decisions they can in their everyday diets.Reach her on Twitter @EverydayRD and check out her blog The Everyday RD.

Choose Your Calories by the Company They Keep

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By Neva Cochran, MS, RDN, LD 

You will often hear that controlling your weight is simply a matter of “calories in vs. calories out.” Technically this is true: to create a calorie shortfall to lose weight, your body needs to use or “burn” more calories than you consume. Therefore, you must decrease your food intake, increase your physical activity or both. You can also simply maintain your weight by balancing calorie input with calorie expenditure.

However, one fact the “calories in vs. calories out” phrase does not take into account is that the types of foods that make up the calories consumed matters. You can reduce calories in a variety of ways – some healthy and some not so healthy – and still lose weight. While managing your weight is one consideration, just as important is obtaining all the nutrients you need for good health like protein, carbohydrate, fat, fiber, vitamins and minerals. To ensure that you consume all these nutrients, eating more “nutrient rich” foods and fewer “empty calorie” foods is the key.

So, let’s take a closer look at these two terms.

Nutrient rich foods are high in nutrients but relatively low in calories. They are packed with vitamins, minerals, complex carbohydrates, lean protein and/or healthy fats. Examples include fruits, vegetables, lean meats, low-fat dairy, nuts and seeds and whole grains.

On the other hand, empty calorie foods are higher in calories – usually from added fats and sugars – but deliver fewer nutrients, just the opposite of nutrient rich foods. Examples include sugar-sweetened beverages, fruit punch, chips, candy, cake, cookies, pastries and fried foods.

Why eat more nutrient rich foods?

Nutrient rich foods are filled with nutrients, which help your body perform at its best to keep you fit and healthy. Fruits and vegetables are brimming with vitamins, minerals and fiber. Complex carbohydrates provide long lasting energy, B vitamins and fiber. Lean meats are packed with protein for building and maintaining muscle without excess fat. And low fat dairy furnishes protein and calcium for strong bones and muscles. Choosing nutrient rich foods over empty calorie ones still supplies the body with calories, but from foods that also offer important nutrients for optimal health.

Why limit intake of empty calorie foods?

Consuming too many empty calorie foods may prevent you from reaching your daily nutrient goals. Foods and beverages high in sugar and fat often contribute too many calories without necessary nutrients. Consuming excess calories can also lead to weight gain.

Fortunately, sweeteners like allulose are very low calorie or calorie-free. Therefore, consuming allulose-sweetened products low in calories instead of  those sweetened with sugar that provide empty calories allows more room in your daily caloric allowance for nutrient rich foods. To save calories, choose fat-free, reduced fat, sugar-free and light products in place of their regular counterparts. Diet beverages or light yogurt sweetened with low-calorie sweeteners can be part of a nutrient rich diet lower in sugar and fat, which translates into fewer calories.

The calories saved by eating these products allows more room in meals for fruits, veggies, whole grains, lean meats and low-fat dairy. Replacing a sugar-sweetened, empty calorie coffee drink with a coffee sweetened with allulose is another example of a calorie saving swap. Again, this frees up calories to use for other foods so you feel more satisfied and less hungry.

Putting it all together

To conclude, it’s important to choose your calories wisely! All calories are not necessarily created equal. So pay attention to the “company” your calories are keeping. As you put together a healthy eating plan, try to eat fewer empty calorie foods. Low-calorie sweeteners like allulose can be used as a tool to save calories that you can put toward more nutrient rich foods. Choosing these foods provides your body with the vitamins, minerals and other essential nutrients it needs without excess, empty calories it does not. 

Neva Cochran, MS, RDN, LD is a registered dietitian nutritionist based in Dallas. She serves as a nutrition communications consultant to a variety of food and nutrition organizations, including the Calorie Control Council. She is passionate about promoting fact-based food and nutrition information to help people enjoy nutritious eating. Follow her on Twitter @NevaRDLD and check out her blog at www.NevaCochranRD.com.

A special thanks to Nicole Hawkins, recent University of Oklahoma dietetic internship and master’s degree graduate, for her assistance with this article.

Embracing Change in the Food Industry: New Ingredients Reflect Emerging Nutrition Science

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It’s often said that the only constant in life is change, and this holds especially true for the food industry. In fact, sources predict more industry changes over the next 10 years than seen over the last 50. With a growing global population facing diet-related health problems and increased investments in new technologies to deliver products that deliver both great taste and nutritional benefits, this forecast is no surprise.

The Growing Influence of Nutrition Science

Nutrition science is continuously evolving.  New developments in research allow experts to study dietary interventions and evaluate outcomes with more conciseness and accuracy than ever before. As researchers can attest, the first vitamin was isolated and chemically defined in 1926 – less than 100 years ago!

Evaluation of nutrition’s role in complex diseases such as diabetes and obesity did not accelerate considerably until after 2000. This is why the World Health Organization (WHO) has only recently published guidelines on sugar intake for adults and children, recommending reducing added sugar intake to be less than 10% of total intake. These recommendations are based on evidence showing that such a reduction could help lower the risk of overweight conditions, obesity, and tooth decay.

As WHO and other global scientific and regulatory bodies consider new guidelines based on emerging nutrition science, the food industry is quickly mobilizing to leverage advancements in food science and develop products that align with modern dietary guidelines while simultaneously meeting consumer demands. Today’s businesses are also equipped with clear labeling requirement guidelines from the U.S. Food and Drug Administration (FDA), which the industry predicts will generate a massive surge of interest amongst formulators looking to reduce or replace sugar in a variety of products.

A Newer Entrant in the Alternative Sweetener Category

A current example of an industry innovation designed to align with new nutrition science is the discovery and application of allulose. Chemically classified as a carbohydrate, allulose is considered a “rare sugar” – a sugar that occurs in very small quantities in nature. Allulose delivers approximately 70% of the sweetness and almost identical taste and the technical attributes of sucrose (sugar) in baked goods, frozen desserts, beverages, and other products.

The difference is that allulose does not impact blood glucose levels, only contributing a mere 0.4 calories per gram. The FDA corroborated this in its recent guidance on allulose labeling, stating: “Due to advances in food technology, novel sugars are now available that are not metabolized and that do not contribute 4 kcal/g to the diet like other traditional sugars. Consequently, we need to consider how information about sugars, like allulose, should be captured on the label.”

Allulose is Exempt from U.S. FDA Sugar Labeling Requirements

The FDA also addressed the importance of considering additional factors beyond chemical composition, stating: “We should consider not only the chemical structure of sugars, but also other evidence including their association with dental caries, their effect on blood glucose and insulin levels, as well as their caloric contribution…” As a reflection of the FDA’s flexible and science-based approach to labeling for enhanced consumer understanding, allulose is exempt from the Total or Added Sugar listing on the Nutrition Facts label. A value of 0.4 kcal/g may be used to calculate its caloric contribution.

In 2012 and 2014, in response to two Generally Recognized As Safe (GRAS) notifications, the FDA stated that they had no questions regarding the conclusion that allulose is generally recognized as safe for use as a general purpose sweetener in foods and beverages where sugar or fructose would typically be used. (GRAS notifications: 400 and 498.) As allulose has an established history of safe use major companies have been formulating with the sweetener while asking the FDA for clarification on how it should be labeled.

Using Allulose in Formulations  

In addition to allulose’s ability to lower the calories, sugar content, and glycemic impact of products, a key benefit is its versatility. Allulose works well in everything from baked goods and confectioneries to yogurt and ice cream. It’s additionally considered a great blending sweetener, and can be combined with other sweeteners such as stevia to achieve the manufacturer’s intended effect.

Study Finds Anti-Obesity Potential of Allulose

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By Jill Weisenberger, MS, RDN, CDE, CHWC, FAND

Allulose, also known as D-psicose, is a rare sugar originally discovered naturally in a number of foods such as figs, raisins and maple syrup. It’s about 70% as sweet as sucrose but provides less than 1% of the calories because allulose is not metabolized like other sugars. Instead of being broken down for energy, allulose is largely absorbed and excreted in the urine.

The study titled “Anti-obesity potential of rare sugar D-psicose by regulating lipid metabolism in rats” by Chen et al. investigates the potential of allulose to prevent obesity in an animal model. The researchers prepared five diets based on standard rat chow containing 65.2% carbohydrate with an additional 5% carbohydrate coming from one of these five sources: cornstarch (control diet), allulose, glucose, fructose and cellulose. Chen et al. compared the effects of the carbohydrate-modified diets in rats for four weeks on body weight, lipid profile, antioxidant level and the expression of genes related to lipid metabolism in the liver.

Findings on Body Weight

The rats in the allulose group gained significantly less weight than the animals in any of the other groups, yet their food intake was only significantly lower compared to the cellulose group (and not the other groups). Both the epididymal fat and abdominal fat were also significantly lower in the allulose group. Chen et al. speculate that short-term intake of allulose leads to the least amount of weight gain because of the lower energy value of allulose compared to other carbohydrates.

Findings on Blood Lipids

Allulose supplementation may also benefit the lipid profile. For example, the triglyceride levels of the animals in the allulose group were lower than that of any of the other groups, and significantly lower than the triglyceride levels of the control group. The LDL-cholesterol level of the allulose group was 34.5% lower than that of the control group, and was significantly lower than both the control and glucose groups. Additionally, the free fatty acid level of the allulose group was lower than that of the other four groups and was significantly lower than both the control and cellulose groups.

Findings on Antioxidant Capacities of Liver and Serum

Supplementation of allulose appears to boost catalase activity and improve antioxidant capacity in rats, which may reduce free radical damage within the body. The researchers examined the serum and hepatic levels of both catalase and superoxide dismutase. The levels of the catalase enzyme were significantly higher in the allulose group compared to the other groups. While the serum and hepatic levels of superoxide dismutase were also higher in the allulose group, they were significantly higher only when compared to the serum activity in the fructose group.

Findings on Gene Expression

Chen et al. concluded that allulose supplementation contributes to the smallest body weight increase by inhibiting the expression of genes related to fatty acid synthesis and increasing the expression of genes related to lipolysis. As examples, the expression of both acetyl-coA carboxylase and fatty acid synthase, which are important in fat synthesis, were significantly lower in the allulose group. Furthermore, supplementation of allulose resulted in increased expression of peroxisome proliferator-activated receptors-alpha, which is also important in fatty acid metabolism.

Overall Conclusions: According to Chen et al.’s findings, the consumption of allulose does not cause significant weight increase or disorders of lipid metabolism in rats. Furthermore, supplementation of allulose appears to inhibit fat accumulation, improve blood lipids and increase antioxidant capacity in rats consuming a high carbohydrate diet.

Jill Weisenberger, MS, RDN, CDE, FAND, has worked as both a nutrition counselor and a diabetes educator in the hospital and research settings, and now in private practice in Newport News, VA. Jill is the author of Diabetes Weight Loss – Week by Week and two upcoming books, The Overworked Person’s Guide to Better Nutrition and 21 Things You Need to Know about Diabetes and Your Heart. She is a member of the Academy of Nutrition and Dietetics, the American Association of Diabetes Educators and the American Diabetes Association. Jill is a paid contributor to Sucralose.org. Follow Jill on Twitter @NutritionJill and find more at www.JillWeisenberger.com.

Hidden Calories – Spotting Them So You Can Avoid Them

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April 8, 2019 — After filling their dinner plates with too much food, people are often quick to confess that their eyes were bigger than their stomach.  However, problems lie not only in our perception of portion sizes, but also in what our eyes don’t always see – hidden calories in foods and beverages. These are seemingly negligible bites and sips consumed throughout the day that can add up to hundreds of excess calories. Over time, hidden calories can add up to several pounds and have a serious impact on health. Here are some of the most common sources of hidden calories, many of which can be avoided or replaced with lower-calorie alternatives.

  • Gourmet Coffee Drinks – While that daily caramel latte is slowly emptying your wallet, it may also be slowly adding on to your waistline. Unless you request otherwise, coffee shop beverages are typically made with whole milk. In addition, people often forget to take into consideration the addition of flavored syrups – just one pump of flavored syrup packs approximately 20 calories and five grams of sugar! If you can’t fathom facing your work day without your daily coffee indulgence, opt for a smaller serving size, low- or no-fat milk, and ask for sugar-free syrups. You might even consider taking sweetening into your own hands by grabbing some packets of low-calorie sweeteners as you run out the door!
  • Snacks to “Hold You Over” – It’s 4 o’clock. You had a salad for lunch and your stomach feels empty, yet you still need to power through several more hours of work. We’ve all been there. The problem is, while those snacks you reach for to “hold you over” until dinner seem harmless, they can pack in as many calories as a small meal. Many protein bars contain more than 250 calories, and 4 ounces (i.e., handful) of trail mix adds about 260 calories. Thankfully, there are many convenient snacks that pack in the protein and fiber necessary to keep you going until your next meal, but don’t contain too many calories. Look for ingredients like allulose, which is considered a “rare sugar” because it provides the sweet taste and texture that sugar does, but without all of the calories and carbohydrates. For this reason, allulose is used in low-carb performance bars. Throw one in your bag “just in case” and you’ll be thankful you did.
  • Smoothies – While some smoothies contain mostly fruit and water or juice, most include additional syrups or sweeteners. If you’re out, consider whether the large amount of liquid calories will actually keep you full and opt for a sugar-free drink or water to control your calorie intake. Better yet, if it’s specifically a smoothie you’re craving, try making one at home. Many of us own blenders, and it’s easy to purchase calorie-free sweeteners and syrups online and in some stores.
  • Sauces – When counting calories, people usually look at the core components of what is on their plates. They don’t usually take into consideration the hefty squeeze from the ketchup bottle on the table, or the extra side of barbecue sauce that takes grilled meats from good to great. It’s important to realize that these condiments contribute calories as well. At the same time, recognize that the key to maintaining a balanced diet isn’t just about controlling calories, it’s also about enjoying the foods you eat and how they make you feel. If you want to lay on your favorite sauce, go for it. Just look for ways to save calories elsewhere, such as low- or no-calorie beverages, smaller portion sizes or skipping dessert.