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A Spoonful of Toxins: Artificial Sweeteners Disrupt Gut Microbiome

By Kristen Schepker, Assistant Editor

Artificial sweeteners can help patients reduce sugar consumption — but new evidence of harm to the microbiome suggests sugar substitutes cause alarming health problems of their own.

A Spoonful of Toxins

In September, researchers at Ben-Gurion University of the Negev (BGU) in Israel and Nanyang Technological University in Singapore published a study in the journal Molecules showing that artificial sweeteners are dangerously disruptive to a healthy gut. artificial sweeteners

The BGU team assessed the relative toxicity of six FDA-approved artificial sweeteners, identifying toxic responses when bacteria representative of the gut microbiota encountered even tiny concentrations of the faux sugars.

Using a panel of bacteria genetically modified to luminesce when exposed to certain toxicants, scientists evaluated the effects of aspartame, sucralose, saccharin, neotame, advantame, and acesulfame potassium-k (ace-k), as well as ten commercial sports supplements containing the sugar substitutes, on the intestinal microbiome. The bacteria panel included three different bioluminescent Escherichia coli strains (TV1061, DPD2544, and DPD2794) engineered to respond to cytotoxicity, amino acids availability, and genotoxicity, respectively. E. coli, an indigenous gastrointestinal microorganism, serves as a model for human gut bacteria (Harpaz, D. et al. Molecules. 2018; 23(10): 2454. DOI: 10.3390/molecules23102454).

Researchers found that all of the sweeteners and supplements, at varying amounts, exhibited toxic effects on the microbiome. They measured bacterial growth and the luminescent signals each sugar substitute produced, showing that different sweeteners triggered different types of toxicity responses.

Ace-K and aspartame, for instance, induced luminescence only in genotoxic sensitive bacteria (DPD2794), indicating the possible genotoxicity of those two sweetening agents. Saccharin, on the other hand, demonstrated higher cytotoxic than genotoxic effects on gut bacteria.

Concentrations as low as 1 mg/mL of the sugary substances caused gut bacteria to become toxic.

A Warning to Athletes

Toxicity testing of the sports supplements generated similar results. A wide range of commercial electrolyte beverages and other nutritional products aimed at athletes are available to consumers today, and many don't realize that the majority of these "health" items contain artificial sweeteners.

While each of the studied supplement mixtures contained a variety of different compounds, all included the addition of at least one artificial sugar to sweeten the product's flavor. The E. coli panel responded uniquely to each sport supplement, but in every case, investigators observed some type of toxicity response.

Owing to the complexity of each individual product, determining whether the artificial sweeteners themselves or some other added ingredient caused the toxic effects was challenging, the authors write. Overall, they argue that the sport mixtures acted primarily by causing damage to cellular membranes.

"While some similarities were found in the cells' responses to the artificial sweeteners, the complicated sport supplements composition limit our understanding and information about the actual role of the artificial sweetener addition. However, the triggered luminescent and affected growth rates indicate that all tested sport supplements were toxic to the bacteria," they concluded.

Questionable Health Benefits

The BGU study is certainly not the first to question the controversial health benefits of artificial sweeteners.  

While research on artificial sugars is still somewhat limited, holistic healthcare practitioners generally view non-natural sweeteners with caution. Nevertheless, the use of sugar substitutes is on the rise – and often, patients consume products without realizing that they contain added sweeteners. Artificial sugars exist throughout the food chain as standalone products or, more insidiously, as additives to countless foods, beverages, and supplements.

Mounting evidence suggests that consuming sugar substitutes adversely affects gut microbial activity, influencing susceptibility to a host of health issues. Studies link artificial sweetener use to the development of cancer, weight gain, metabolic disorders, glucose intolerance, and type 2 diabetes.

Ironically, patients with diabetes or obesity often use sugar substitutes as tools for curbing real sugar consumption – but both obesity and type 2 diabetes are more prevalent among individuals who drink more artificially sweetened beverages than healthier alternatives, despite the fact that the sugar-free compounds elicit no apparent insulin response.

A 2012 Crohn's disease study indicated that the commercial sugar substitutes Splenda (sucralose, dextrose, and maltodextrin) and Equal (aspartame, dextrose, and maltodextrin) promote the adhesion and growth of E. coli, an activator of inflammation in Crohn's patients. The study's authors found that in particular, the ubiquitous dietary additive maltodextrin appeared to promote gut dysbiosis, concluding that the sweetener can worsen the health of patients with Crohn's and other chronic diseases affecting the intestines.

More recently, a 2017 report from the ongoing Framingham Heart Study showed that drinking as little as a single can of sugar-free soda per day is associated with higher risks of both having a stroke and developing dementia. Significantly, no associations were found between the consumption of soft drinks sweetened with natural sugars and stroke or dementia risk.

"Natural" Alternatives

For those looking to reduce or avoid the use of sugar-free products, a growing number of natural sweeteners can be used instead.

Supplementing Dietary Nutrients—A Guide for Healthcare Professionals, a 2014 book by Thomas G. Guilliams, PhD, offers one comprehensive source of information on natural sweeteners commonly used in therapeutic products like functional foods, powders, bars, and chewable tablets. "While controversy still remains about the risk of consuming artificial sweeteners, we recommend they be avoided by all individuals," Guilliams writes, outlining several sugarless alternatives. 

Stevia, extracted from the sweet leaves of the stevia plant, is one popular option. More than 200 times as sweet as sugar, stevia leaf extract provides zero calories per serving and has an estimated glycemic load of zero.

Monk fruit extract, similar to stevia, is another potent zero-calorie natural choice.

Other naturally sweet substances fall into more of a grey area. Though they come from plant or animal sources, some sugar alternatives are produced synthetically – or may never have been intended for use in the food supply to begin with.

High fructose corn syrup, for instance, is technically derived from corn – but the heavily processed sweetener contains a huge amount of fructose which, if eaten in excess, may contribute to several metabolic disorders.

Trehalose, a naturally occurring disaccharide present in the cells of many non-mammalian species, is also used as a food additive. Insects like bees and grasshoppers, as well as shrimp, oysters, sea algae, sunflower seeds, some mushrooms, beer, bread, and other foods produced by using baker's or brewer's yeast, all contain small amounts of trehalose.

Synthetic trehalose is an ingredient added to numerous products, from dried and frozen foods to instant noodles and rice to nutrition bars, fruit fillings, jams, sugar coatings, bakery cream, and processed seafood and fruit juices. It can be tough to avoid – and its silent presence might contribute to huge health consequences.

In a January 2018, researchers published a study in the journal Nature proposing that dietary trehalose stimulates the growth of certain strains of Clostridium difficile bacteria in the gut. A concerning antibiotic-resistant superbug, C. difficile causes infections marked by life-threatening diarrhea and severe inflammation of the colon. The number of reported cases of the illness have jumped significantly over the last two decades, a trend that aligns with the FDA's granting of GRAS (Generally Recognized As Safe) status to trehalose in 2000, the Nature paper's authors point out (Collins, J. et al. Nature. 2018; 553(7688): 291–294). 

No Better Than Real Sugar

It is important for physicians to consider that, whether or not they recommend the use of sugar substitutes, some of their patients are likely eating, drinking, or supplementing with artificial sweeteners. Ample evidence now supports the position that fake sugars are not only no better for us than real sugar, but trigger major health complications of their own.

Educating people on the ways in which diet affects the microbiome and influences disease risk is an invaluable gift integrative clinicians are well-poised to offer their patients. Healthcare practitioners can teach patients to review food and nutrition labels and learn to avoid consuming undesirable ingredients without their knowledge. Along with patients with chronic illness, athletes who supplement their diet with products to improve physical performance should know the harms associated with nutritional formulas containing artificial sweeteners. The Molecules paper's authors explain that average consumption of sugar substitutes is higher in athletes, placing them at greater risk for any potential danger. 

If the physical health concerns aren't enough to turn patients off from fake sugar, scientists also now recognize artificial sweeteners as emerging environmental pollutants. Resistant to wastewater treatment processes, the sugary chemicals are continuously re-introduced into water environments, including drinking waters and groundwater aquifers. At this time, it's unknown how exactly the escaped artificial sweeteners will affect aquatic organisms and ecosystems in the long term. 

Until further research clarifies the full public and planetary health impacts of the many different sugar substitutes, patients should approach alternative sweeteners with great caution. Avoiding sugar sounds like a healthy choice — but sugar-free sweeteners really aren't as sweet as they may appear.

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Gottlieb Resignation Leaves Key Supplement Rules in Limbo

By Erik Goldman, Editor

FDA Commissioner Scott Gottlieb’s surprise resignation earlier this month sent shockwaves through the natural products industries. His departure at the end of March will leave two key aspects of dietary supplement regulation in limbo: the legality of CBD supplements, and the possibility of a major revision of the Dietary Supplement Health and Education Act (DSHEA).

Choline, Carnitine & the Heart: Is TMAO Really a Risk Factor?

By Russell Jaffe, MD, Contributing Writer

Recently, I was asked if I had any concerns about elevated levels of TMAO—trimethylamine N-oxide--with a diet high in eggs. This is a reasonable question given that elevated TMAO levels have been linked to increased cardiovascular disease and stroke. As with most physiologic functions, however, the answer is nuanced and highly individualized. It’s not a simple “good or bad” subject.

Early Childhood Trauma Raise Adolescent Obesity Risk

By Kristen Schepker, Assistant Editor

A new study shows that early childhood trauma correlates strongly with higher rates of adolescent obesity. The  findings offer important insights into the complex etiology of pediatric obesity which, researchers believe, could stem partly from traumatic psychosocial factors early in life.

Using data from the statewide Minnesota Student Survey (MSS), a team of University of Minnesota researchers examined the association between adverse childhood experiences––or ACEs––and the development of overweight or obesity later in life. ACEs include physical or sexual abuse, neglect, household substance abuse, or the death or incarceration of a close relative, along with exposure to extreme violence.ace pyramid lrgACE Pyramid from the 1998 ACE Study

The investigators analyzed information collected from over 105,000 8th, 9th, and 11th grade students from across the state, making this it the largest study to date of ACEs and their potential role in the etiology of obesity.

They grouped the students based on their height and weight (BMI) into one of five categories: underweight, normal weight, overweight, obese, or severely obese. They also looked at the adverse events self-reported by the kids, including physical abuse, sexual abuse, psychological abuse, familial substance abuse, domestic violence, and parental incarceration.

Controlling for other variables, they found that adolescents who had experienced at least one ACE were  much more likely to be overweight, obese, or severe obesity than their peers who had not experienced ACEs.

As reported in The Journal of Pediatrics, youth who experienced one adverse childhood event were 1.2 times, 1.4 times, and 1.5 times more likely, respectively, to be overweight, obese, and severely obese when compared with those who did not disclose any ACEs (Davis, L. et al. J Ped. 2019; 204: 71–76e). 

Adiposity risk also increased with the number and frequency of ACEs. Adolescents with six ACEs were respectively 1.5, 2.0, and 4.24 times as likely to be overweight, obese, and severely obese compared to students reporting no ACEs. Notably, they found no relationship between ACEs and underweight in this data set.

Child health professionals across disciplines should take note of these patterns. 

Growing Obesity Rates

Pediatric obesity rates in the US are soaring. According to the Centers for Disease Control and Prevention (CDC), the percentage of American children and adolescents affected by obesity has more than tripled since the 1970s. National Center for Health Statistics data from 2015-2016 show that nearly one in five school-aged children and adolescents aged 6 to 19 years were obese. 

Laurel Davis PhDLaurel Davis, PhD, University of MinnesotaWhile the ACE study did not examine potential mechanisms for the relationship between trauma and obesity, its lead author, Laurel Davis, PhD, research associate in the Department of Pediatrics at the University of Minnesota Medical School, said that there are likely several possible explanations––with stress being a key culprit.

"First, stress has been associated with changes in eating behaviors in both human and animal studies," she proposed. "Second, stress has significant effects of the body's hormonal and regulatory systems, particularly the hypothalamic-pituitary-adrenal (HPA) axis, which has been implicated in weight status."

"Finally," Davis said, "it's likely that the same factors in a youth's context that predispose them to ACEs also have effects on their access to nutritious food. For example, parental incarceration is associated with reductions in family income, which might cause food insecurity." Davis's team is planning future studies to evaluate some of these hypotheses.

Trauma Predicts Poor Health

A University of Minnesota research brief announcing the study indicates that, like adults, youth who are overweight or obese are at higher risk for developing additional related health problems, each with their own lifelong consequences. Depression, high blood pressure, metabolic disorders, sleep apnea, diabetes, and fatty liver disease are are just some of those conditions. 

Figuring out what causes obesity is a question that has long challenged many researchers. Particularly in children, it's easy to focus on the physical factors that contribute to weight status: diet, food quality, exercise and physical activity.

This new study sheds light on the often overlooked psychosocial determinants that play crucial roles not just in obesity, but in overall health and wellness.

The idea that trauma in the form of ACEs can drive obesity and other diseases is a relatively new one, but Davis' group is not the first to explore the connection. The landmark Adverse Childhood Experiences (ACE) Study, published in 1998 in the American Journal of Preventive Medicine, was the first to formally introduce the concept into the medical literature.

A collaboration between the CDC and Kaiser Permanente, this project utilized data collected in 1995–1997 from more than 9,500 Kaiser members at a San Diego clinic. Until Davis' publication this year, it was one of the nation's largest investigations of childhood traumas and their future health consequences.

In the study, physicians compared patients' reported childhood experiences of abuse and neglect against their current health status and behaviors. They identified seven core ACE categories––psychological, physical, or sexual abuse; domestic violence; living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned––and uncovered "a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults" (Felitti, J. et al. Am J Prev Med. 1998; 14(4): 245–258).

Patients who experienced more than one ACE were at higher risk for multiple health threats later in life, including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease.

It's easy to focus on the physical factors that contribute to weight status: diet, food quality, exercise and physical activity.This new study sheds light on the often overlooked psychosocial determinants that play crucial roles not just in obesity, but in overall health and wellness.

These studies underscore the fact that health or illness are determined by far more than one's genetics or underlying biology alone. With regard to weight and obesity risk, forces like socioeconomic status, quality of life, and mental health conditions like depression and anxiety all have significant influence.

Hidden Danger 

The new University of Minnesota study reveals that adverse childhood events are far more prevalent than many clinicians might realize.

The authors say that their findings parallel a recent report from national surveys showing that nearly half of all US children have experienced at least one ACE. Between 40%-50% of youth in their sample who reported having overweight, obesity, or severe obesity also reported at least one ACE. The more ACEs a child encounters, the higher his or her disease risk becomes. In some cases, the consequences are immediate.

"This study adds to our understanding of childhood overweight and obesity by showing that the relationship between ACEs and weight problems is evident even in adolescence," said Davis.

Prior studies exploring the associations between ACEs and obesity have mostly involved adult participants, and they generally suggest a strong association between childhood exposure to ACEs and obesity in adulthood. By utilizing anonymous reports from adolescents––which, according to Davis, are found to be highly reliable––she and her colleagues were uniquely able to clarify the impact of ACEs in the time period shortly after they actually occurred.

"The advantage of asking youth to report their ACEs is that it removes a potential source of bias: caregiver reluctance to report," she explained. Many ACEs are either perpetrated by parents––as in the case of physical or emotional abuse––or a cause of shame or stigma for the family, like mental illness or involvement in the criminal justice system. Allowing youth to directly report their own ACEs obviates this problem, Davis said.

Screening Children for ACEs

The mounting evidence from ACE studies compels health practitioners to recognize the strong relationship between ACEs and disease risk, beginning in adolescence and extending into adulthood.

With appropriate education and awareness, ACEs are both preventable and treatable.

"Doctors should be aware that ACEs have the potential to compromise health and wellbeing in childhood and throughout the lifecourse," Davis encouraged, adding that "addressing [a] patient's ACEs is a critical part of health promotion."

She also suggests that "due to the high prevalence of ACEs, clinical training programs should consider adding training in this area for new child health trainees, so that clinicians are prepared to screen for and respond to their patients' disclosure of ACEs."

Davis and her colleagues have not examined the efficacy of specific ACE assessment or treatment protocols, but they urge practitioners who work with young people to consider standardized screening for ACEs and to make referrals for appropriate psychosocial interventions as needed.

A number of ACE screening tools exist. A 2017 paper published in Academic Pediatrics identified and analyzed 14 different  methods, including a new ACE measure that's now part of the larger National Survey of Children's Health (NSCH-ACEs).

"As for the types of services a physician should refer to, that is a complicated choice that should be based on a number of decisions, including but not limited to the type, timing, and severity of the ACE, the family's context and resources, their capacity to engage in services, and the types of services that are available in the community in which the child lives," Davis pointed out.

"Our most basic recommendation is that physicians work in collaboration with other professionals––social workers, community mental health workers––to connect families to appropriate services." She added that "treatments that involve children's caregivers are highly efficacious."

The CDC offers a list of ACE resources that include training materials, journal articles, and other educational tools for practitioners, families, and communities alike.

Most importantly, clinicians should be aware that "ACEs have a profound impact on both mental and physical health. Early life adversity is one of the most powerful social determinants of health across the lifecourse," Davis said. "For almost every condition for which the association has been examined, ACEs have been found to be related to poorer health." 

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Functional Formularies Offers Organic, Plant-Based Options for Tube-Feeding

By Ellen Kanner, Contributing Writer

A small independent company based in Ohio launched a feeding tube formula called Liquid Hope, comprised entirely of organic whole foods like chickpeas, sprouted quinoa, almond butter, turmeric, kale, sweet potato, and other high-energy, anti-inflammatory ingredients. Unlike most conventional enteral nutrition formulas, Liquid Hope is free from sugar, corn syrup, omega-6 laden oils, and dairy ingredients. It is making a profound difference in the lives of many patients. 

Hemp & CBD: Evidence, Evangelism & Extreme Exuberance

By Erik Goldman, Editor

If you are confused about the therapeutic value of hemp oil, cannabidiol (CBD), and other cannabis-related substances, and you’re scratching your head trying to figure out what’s legal and what’s not, that’s good: It means you’re paying attention.  Yes, there is some evidence, but there's also a lot of evangelism. Clinicians face the challenge of separating the scientific realities from the hype. 

Cannabis: State of the Science

By Erik Goldman, Editor

Is there any solid science to support the use of phytocannabinoids in clinical practice? The answer is yes….and no.

It depends on how you define “cannabis” and “cannabinoids;” whether you’re talking about inhaled (ie, smoked or vaped), ingested, or sublingual delivery; and of course, which diseases you’re considering.

Cannabis & Hemp: A Regulatory Update

By Erik Goldman, Editor

The year 2018 was a landmark in the history of hemp and cannabis in the US. It was the year the FDA approved the first natural cannabis-derived prescription drug, and Congress passed a Farm Bill that included provisions legalizing cultivation of, and interstate commerce in, low-THC hemp. But the laws and regulation around hemp and cannabis remain a confusing patchwork, and some states are taking regulatory actions that run counter to the new federal provisions.

Cannabis, Hemp, Marijuana: What's in a Name?

By Erik Goldman, Editor

Amid the current rage for all things cannabis, there is a lot of confusion about the terminology used to describe this plant and compounds extracted from it.

Part of that confusion arises from the Farm Bill of 2018, which changes some federal definitions. These changes have major implications for legal and regulatory policy.  Here’s a guide to common cannabis-related terms and their current definitions.