Alternative sweetener sorbitol linked to liver disease

 

Sweeteners such as aspartame, found in Equal packets, sucralose (Splenda), or sugar alcohols are often seen as healthier alternatives to food with refined sugar (glucose).

But that assumption is being challenged with new scientific research, including the recent finding that the sugar alcohol sorbitol is not as harmless a sugar substitute as once thought.

The study, published recently in Science Signaling, follows a line of research detailing the harmful effects of fructose on the liver and other systems from the lab of Gary Patti, at Washington University in St. Louis.

Patti, the Michael and Tana Powell Professor of Chemistry, in Art & Sciences, and of genetics and medicine, at WashU Medicine, previously has published research about how fructose processed in the liver can be hijacked to supercharge cancer cells. Previous research also has found that fructose is a key contributor to steatotic liver disease, affecting 30% of the adult population worldwide.

The most surprising finding from the current work is that because sorbitol is essentially “one transformation away from fructose,” it can induce similar effects, Patti said.

The research involved experiments with zebrafish demonstrating that sorbitol, often used in “low-calorie” candy and gum, and commonly found in stone fruits, can naturally be made by enzymes in the gut and eventually converted into fructose in the liver.

Patti’s team found there are many roads to fructose in the liver, and potential detours, depending on a person’s sorbitol and glucose consumption patterns, along with the bacterial populations colonizing their gut.

For starters, although most of the research on sorbitol metabolism has focused on its production due to glucose overload in pathological settings such as diabetes, sorbitol can be naturally produced in the gut from glucose after eating, Patti said.

The enzyme that produces sorbitol has a low affinity for glucose, so glucose levels must be high for it to take effect. That is why sorbitol production has primarily been associated with diabetes, where blood glucose levels can become elevated. But, even in healthy settings, glucose levels in the gut become high enough after feeding to drive sorbitol production within the intestine, according to the team’s zebrafish experiments.

“It can be produced in the body at significant levels,” said Patti. “But if you have the right bacteria, turns out, it doesn’t matter.”

Sorbitol-degrading Aeromonas bacterial strains convert the sugar alcohol into a harmless bacterial byproduct.

“However, if you don’t have the right bacteria, that’s when it becomes problematic. Because in those conditions, sorbitol doesn’t get degraded and as a result, it is passed on to the liver,” he said.

Once in the liver, it is converted to a derivative of fructose. It’s important to determine if alternative sweeteners are providing a healthy alternative to table sugar since people with diabetes and other metabolic disorders may be relying on them as “sugar free” products.

Gut bacteria do a good job of clearing sorbitol when it is present at modest levels, such as those found in fruit. But problems arise when sorbitol quantities become higher than what gut bacteria can degrade. This can occur when excessive amounts of glucose are consumed in the diet, which lead to high levels of glucose-derived sorbitol, or when dietary sorbitol itself is too high.

The more glucose and sorbitol consumed, then, even if someone has the friendly bacteria that clears it, those gut microbes may be overwhelmed with the task.

Avoiding both sugar and alternative sweeteners is increasingly complicated, as many foods are packed with multiple varieties of all the above. Patti was bemused to discover his own favorite protein bar was chock full of sorbitol.

The lab will need to do more research to understand the specific mechanisms for how bacteria clears sorbitol, but the basic idea that these sugar alcohols, called polyols, are harmlessly expelled, may not hold true.

“We do absolutely see that sorbitol given to animals ends up in tissues all over the body,” he said.

Bottom line: it’s becoming more apparent that “there is no free lunch” when trying to find sugar alternatives, with many roads leading to liver dysfunction.

Vitamin C from food boosts collagen levels in skin

 A breakthrough study from researchers at the University of Otago, Faculty of Medicine – Christchurch Ōtautahi, has found that collagen production and skin renewal directly respond to the amount of vitamin C we eat.  

The study, published in the international Journal of Investigative Dermatology, shows that skin vitamin C levels are closely tied to levels of the vitamin in the blood (plasma) and can be boosted by increasing fruit intake.  

Carried out on two dozen healthy adults in both Aotearoa New Zealand and Germany, the study shows that boosting plasma levels by consuming two vitamin C-rich SunGoldTM kiwifruit per day increases the amount of the vitamin in the skin, improving skin thickness (collagen production) and stimulating renewal and regeneration of the outer skin layer.  

Lead author, Professor Margreet Vissers from Mātai Hāora – Centre for Redox Biology and Medicine, within the Department of Pathology and Molecular Medicine, says the strength of the association between skin thickness and vitamin C intake is “compelling”. 

“We were surprised by the tight correlation between plasma vitamin C levels and those in the skin – this was much more marked than in any other organ we have investigated,” Professor Vissers says. 

“We are the first to demonstrate that vitamin C in the blood circulation penetrates all layers of the skin and is associated with improved skin function. I am very proud of my team and excited about what the data is telling us.” 

Professor Vissers says the study results suggest that beauty really does come from within, supporting your skin function from the inside-out by delivering vitamin C to the skin the way nature designed it – via the bloodstream.  

“We know that vitamin C is required for collagen production. This fact has inspired the addition of vitamin C to many skin cream formulations. However, vitamin C is highly water soluble and poorly absorbed through the outer skin barrier. Our study shows that the skin is extremely good at absorbing vitamin C from the blood circulation. Uptake into the outer epidermal skin layer also seems to be prioritised,” she says. 

Funded by New Zealand company Zespri International along with a University of Otago Research Grant, the study comprised two stages. The first stage established the association between plasma and skin vitamin C levels, using healthy skin tissue from patients undergoing elective surgical procedures at Te Whatu Ora Canterbury (with support from the Otago campus’s He Taonga Tapu - Canterbury Cancer Society Tissue Bank).  

The second stage involved a before-and-after, dietary vitamin C intervention study at two sites (in Christchurch and Germany), each with 12 healthy participants.  

“All were instructed to consume two Kiwi Gold kiwifruit daily - the equivalent of 250 micrograms of vitamin C - for eight weeks. We then collected skin samples before and after the intervention, with separate analyses allowing us to look at the skin basal layers in Christchurch and the outer dermal skin layer and skin function tests in Germany,” Professor Vissers explains.  

The German participants were recruited and tested by the SGS Institute Fresenius in Hamburg – their lab having the technical ability to collect the outer dermal skin layer (the blister “roof”). The Institute measured skin sample regeneration - including ultrasound tested measures of skin thickness, elasticity UV protection and renewal of epidermal cells - giving a complete picture of skin function. 

“The other really substantial finding showed a significant increase in the participants’ skin thickness levels, reflecting collagen production and an upsurge in the regeneration of their epidermal cells, in other words skin renewal,” Professor Vissers says. 

 She says SunGoldTM kiwifruit was chosen for the trial due to its proven high vitamin C levels, but it’s anticipated that other foods rich in vitamin C, particularly fresh fruit and vegetables such as citrus, berry fruit, capsicums and broccoli, would have similar beneficial effects.  

“We suggest that increasing your dietary vitamin C intake will result in effective vitamin C uptake into all compartments of the skin,” Professor Vissers says. 

“The important thing is to keep your plasma levels optimal, which we know can be easily achieved in a healthy person with a vitamin C intake of around 250mg per day. The body however does not store the vitamin, so we recommend 5+ a day, every day, with one of those five being a high vitamin C food, as a good habit to cultivate.” 

Foods rich in vitamin C include fruits like oranges, strawberries, kiwi, papaya, and cantaloupe, as well as vegetables such as bell peppers (especially red), broccoli, and Brussels sprouts. Other good sources are tomatoes, blackcurrants, and potatoes

Gas stoves and nitrogen dioxide exposure

 

Peer-Reviewed Publication

PNAS Nexus

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Indoor (gold) and outdoor (blue) average nitrogen dioxide exposures.

view more 

Credit: Kashtan et al.

Twenty-two million Americans would no longer be breathing in unhealthy levels of nitrogen dioxide if they switched from gas and propane stoves to electric stoves. Robert Jackson and colleagues combined outdoor air quality data with estimates of indoor nitrogen dioxide emissions from stoves in more than fifteen cities. As outdoor air quality improves, stoves become an increasingly important source of exposure. According to the World Health Organization, health risks to the respiratory system increase at levels above 5.2 parts per billion by volume. Taking indoor and outdoor sources together, the authors found that average total residential long-term nitrogen dioxide exposure is approximately 10 parts per billion by volume for people with gas stoves and approximately 8 parts per billion by volume for those with electric stoves. For households in the 95th percentile of gas stove use, which corresponds to using multiple gas burners and a gas oven for multiple hours a day, stoves account for more than half of total nitrogen dioxide exposure. The authors estimate that approximately 22 million people whose outdoor nitrogen dioxide exposure falls below World Health Organization guidelines exceed those guidelines due to gas stove use. According to the authors, the study’s ZIP-code-level exposure maps could help identify regions to prioritize for indoor and outdoor air quality interventions, particularly in lower-income communities.

Evidence lacking for medical cannabis in most conditions

 

Review finds limited support for cannabis as a medical treatment, except for certain conditions such as pediatric seizures and chemotherapy side effects

Medical cannabis lacks adequate scientific backing for most of the conditions it is commonly used to treat, including chronic pain, anxiety and insomnia, according to a comprehensive review led by UCLA Health.

The paper, published in JAMA, reviewed more than 2,500 articles published from January 2010 through September 2025 including randomized clinical trials, meta-analyses and clinical guidelines. More than 120 studies were prioritized based on their large samples, recency, topics covered and relevancy. The findings come as medical uses for cannabis and cannabinoids such as CBD have grown in popularity, with 27% of people in the U.S. and Canada having reported using it for various purposes such as pain relief, anxiety and sleep problems, according to a 2018 survey.

The review’s first author Dr. Michael Hsu of UCLA Health said there is a gap in understanding between the public and the most recent scientific evidence on its purported medical benefits.

“While many people turn to cannabis seeking relief, our review highlights significant gaps between public perception and scientific evidence regarding its effectiveness for most medical conditions” said Hsu, health sciences clinical assistant professor at the UCLA Health Department of Psychiatry and Biobehavioral Sciences. “Clear guidance from clinicians is essential to support safe, evidence-based decision-making when discussing medical cannabis with their patients.”

The review confirmed that pharmaceutical-grade cannabinoids approved by the U.S. Food and Drug Administration have demonstrated effectiveness but only in a narrow range of conditions. These include medications for HIV/AIDS-related appetite loss, chemotherapy-induced nausea and vomiting and certain severe pediatric seizure disorders such as Dravet syndrome and Lennox-Gastaut syndrome.

For most other conditions, the evidence remains either inconclusive or lacking, the review found. While more than half of people who use medical cannabis report using it for chronic pain, current clinical guidelines recommend against cannabis-based medicines as first-line treatment for chronic pain.

The review also highlighted potential health risks associated with cannabis use. Longitudinal data from adolescents indicated that high-potency cannabis may be linked to increased rates of psychotic symptoms (12.4% versus 7.1% for low-potency) and generalized anxiety disorder (19.1% versus 11.6%).

About 29% of people who use medical cannabis also met criteria for cannabis use disorder. Daily use of cannabis, particularly use of inhaled and/or high-potency products, may be associated with cardiovascular risks, including higher rates of coronary heart disease, heart attack and stroke compared to non-daily use.

The review emphasizes that clinicians should carefully screen patients for cardiovascular disease and psychotic disorders, evaluate potential drug interactions and assess whether the risks outweigh the benefits before considering THC-containing products for medical purposes.

“Patients deserve honest conversations about what the science does and doesn't tell us about medical cannabis,” Hsu said.

The authors noted several limitations of the review. The paper was not a systemic review, and it did not conduct a formal risk of bias assessment of the included studies. Several studies in the review were observational and may be subject to confounding. Additionally, recommendations from clinical trials may not apply to all patients due to variations in their design, patient characteristics and cannabis products tested.

“Further research is crucial to better understand the potential benefits and risks of medical cannabis. By supporting more rigorous studies, we can provide clearer guidance and improve clinical care for patients,” said Dr. Hsu.

Calcium supplementation has no effect on pre-eclampsia

An updated Cochrane review has found that calcium supplementation has no effect on pre-eclampsia, challenging long-held assumptions about the role of calcium in preventing hypertensive disorders in pregnancy.

Researchers from Stellenbosch University have found strong evidence from large trials that calcium supplementation during pregnancy does not reduce the risk of pre-eclampsia.

Pre-eclampsia is a life-threatening condition that can affect women in the second half of their pregnancy. It can be fatal or cause lifelong complications for both mother and baby. Pre-eclampsia is characterised by new onset high blood pressure with end-organ injury. The only cure is to deliver the baby. If the mother develops pre-eclampsia with life-threatening complications, then pre-term delivery is the only option. 

Calcium supplementation has long been considered a potential preventive measure, especially in settings with low calcium intake. Current World Health Organization (WHO) guidelines recommend daily calcium supplementation in such populations. However, evidence supporting this approach has always been mixed, and this review raises further doubts.

Findings cast doubt over benefits of calcium during pregnancy

The updated review included 10 randomized controlled trials with 37,504 participants, looking at the effect of calcium supplementation compared to placebo and comparing high- versus low-dose supplementation. 

Results show that there is high certainty evidence from large trials that calcium supplementation during pregnancy has no effect on preventing pre-eclampsia. 

Even when comparing low and high doses of calcium, outcomes remained largely unchanged. Maternal deaths were rare in the studies, and evidence on other critical outcomes such as neonatal death and severe complications was highly uncertain.

“By applying rigorous and transparent review methods, we found no meaningful difference in key outcomes such as pre-eclampsia, maternal death, preterm birth or neonatal mortality,” says Anke Rohwer, author of the review. “Many of the older studies were of very low quality, and re-evaluating them was essential to ensure that current guidance is based on reliable, up-to-date evidence.”

Untrustworthy and small studies pollute earlier evidence

A previous review update had included far more studies, some of which are now excluded due to changes in eligibility criteria, lack of trustworthiness, or methodological flaws. Earlier analyses that included these small or unreliable studies suggested a stronger protective effect of calcium supplementation.

The authors highlighted that small-study effects and publication bias strongly influenced earlier conclusions. Once these biases were addressed, the apparent benefits of calcium supplementation disappeared. 

“Our updated analysis shows that once you account for issues like small-trial effects and publication bias, the evidence supporting calcium supplementation to prevent pre-eclampsia simply doesn’t hold up,” says Professor Catherine Cluver, co-author of the review. “This marks a major shift from earlier reviews, and it’s crucial that clinicians and policymakers understand how much the evidence base has changed.”

For years, calcium supplementation has been recommended as a preventive measure, especially in populations with low dietary calcium intake. However, this updated review suggests that such benefits may be far less significant — and potentially absent — once untrustworthy evidence is removed.

“This review highlights the importance of applying trustworthiness checks to primary research. Unreliable trials can skew the results of systematic reviews and distort scientific consensus,” adds Professor Cluver. “After excluding unreliable studies, we found that the supposed benefit of calcium supplementation on pre-eclampsia disappeared. We are now show that calcium supplementation does not prevent pre-eclampsia, based on large, reliable trials."

The authors assessed trustworthiness of included studies using the TRACT checklist. Similar tools have since been developed, such as INSPECT-SR,  designed to identify problematic studies. Problematic studies include those affected by human error or research misconduct, where reviewers are not confident that the results are reliable. 

---

Journal

Cochrane Database of Systematic Reviews

DOI

10.1002/14651858.CD001059.pub6 

Changing the sweet taste of someone’s diet has no impact on their sweet tooth or health

Changing the amount of sweetness in a person’s diet has no impact on their liking for sweet foods, the results of a new trial suggest.

The results also showed no difference in indicators of cardiovascular disease or diabetes risk between people who increased or decreased their intake of sweet-tasting foods over a six-month period. 

The research team suggest that consequently public health organisations may need to change their current advice on reducing sweet food consumption to tackle the obesity crisis.  

The study was carried out by Wageningen University and Research in the Netherlands and Bournemouth University in the UK. The results have been published in the American Journal of Clinical Nutrition.

“People have a natural love of sweet taste which has led many organisations, including the World Health Organisation, to offer dietary advice on reducing the amount of sweetness in our diets altogether,” said Katherine Appleton, Professor in Psychology at Bournemouth University and corresponding author for the study. “However, our results do not support this advice, which does not consider whether the sweet taste comes from sugar, low calorie sweeteners, or natural sources.” she added. 

During the trial, 180 participants were split into three groups. One group consumed a diet containing a high amount of sweet-tasting food, a second group consumed a low amount and a third consumed an average amount. The sweetness in the foods provided for their diets came from a combination of sugar, natural sweetness or low-calorie sweeteners.

After one, three and six months, participants were surveyed on whether their liking and perception of sweet foods had changed. They were also weighed and provided blood and urine samples to measure any changes in their diabetes risk and cardiovascular health. 

At the end of the trial, the researchers found no significant differences in any of the measures across the three groups. Participants also reported a spontaneous return to their previous intake of sweet foods after the six months.

Based on their results, the study team are recommending that public health organisations may need to change their current advice on reducing sweet foods to tackle overweight and obesity.  

“It’s not about eating less sweet food to reduce obesity levels,” Professor Appleton said. “The health concerns relate to sugar consumption. Some fast-food items may not taste sweet but can contain high levels of sugar. Similarly, many naturally sweet products such as fresh fruit and dairy products can have health benefits. Public advice therefore needs to concentrate on how people can reduce the amount of sugar and energy-dense foods they consume,” she concluded. 

---

Journal

American Journal of Clinical Nutrition

DOI

10.1016/j.ajcnut.2025.09.041 Å

Polyphenol-rich diets linked to better long-term heart health

 People who regularly consume polyphenol-rich foods and drinks, such as tea, coffee, berries, cocoa, nuts, whole grains and olive oil, may have better long-term heart health.

The research, led by King’s College London, found that those with higher adherence to polyphenol-rich dietary patterns had lower predicted cardiovascular disease (CVD) risk.

Polyphenols are natural compounds found in plants that are linked to various health benefits, including improved heart, brain, and gut health.

The study, published today in BMC Medicine, followed more than 3,100 adults from the TwinsUK cohort for over a decade, found that diets rich in specific groups of polyphenols were linked to healthier blood pressure and cholesterol profiles, contributing to lower CVD risk scores.

For the first time, the researchers also analysed a large number of metabolites in the urine that are produced when the body breaks down polyphenols.

These biomarkers confirmed that individuals with higher levels of polyphenol metabolites—especially those derived from specific groups of polyphenols, flavonoids and phenolic acids—had lower cardiovascular risk scores. They also had increased HDL cholesterol, also know as ‘good’ cholesterol.

The study used a newly developed polyphenol dietary score (PPS) to capture intake of 20 key polyphenol-rich foods commonly consumed in the UK, ranging from tea and coffee to berries, olive oil, nuts, and whole grains.

This score showed stronger associations with cardiovascular health than estimates of total polyphenol intake, likely because it captures overall dietary patterns rather than individual compounds.This finding suggests that considering the whole diet provides a more accurate picture of how polyphenol-rich foods work together to support long-term heart health.

Professor Ana Rodriguez-Mateos, senior author and Professor of Human Nutrition at King’s College London, said: “Our findings show that long-term adherence to polyphenol-rich diets can substantially slow the rise in cardiovascular risk as people age. Even small, sustained shifts towards foods like berries, tea, coffee, nuts, and whole grains may help protect the heart over time.”

Dr Yong Li, first author of the study, added: “This research provides strong evidence that regularly including polyphenol-rich foods in your diet is a simple and effective way to support heart health. These plant compounds are widely available in everyday foods, making this a practical strategy for most people.”

The researchers note that while cardiovascular risk naturally increases with age, higher polyphenol intake was associated with a slower progression of risk over the 11-year follow-up period. They also emphasise the need for future dietary intervention studies to further validate these associations.