A Review of Sweeteners

A Review of Sweeteners

Below is a list of the sweeteners discussed during the Podcast

1. Sugar (full calorie)

2. Low cal sweeteners 

3. No cal sweeteners

Sugar (castor, brown)





Sucralose (Splenda)

Coconut Sugar


Saccharin (Benzoic sulfimide)






Sweeteners should be avoided. And in my little ‘unreal world’ where we all eat ‘perfect’ and hit the gym twice a week, sweeteners don’t exist and aren’t needed.


OK, back to the real world (unfortunately) and sweeteners do exist and no one eat perfectly. Sure, we try to eat well, and this is where artificial sweeteners came from. The thought was that if you can flick calorific sugar out of your diet and instead just eat artificial sweeteners that have no calories, everyone would be trim and there would be no need to give up on ‘sweets’.


Well, unfortunately over a century after the first sweetener was discovered while making coal tar (nope, I am not kidding), we are now learning these ‘safe’ agents may not be so safe after all.  So go ahead and drink/eat/use these agents but know the facts about what is going on in your body.


Where do we taste the different sweeteners on the tongue?


Bioactive Compounds in Honey, Propolis, and Royal Jelly Honey, propolis, and royal jelly are highly rich in bioactive compounds. Essential and nonessential compounds, such as polyphenols and vitamins occurring naturally as part of food chains, are considered bioactive. These compounds are naturally present in food and confer useful health benefits. Phenolic compounds are bioactive compounds. Phenols are defined as organic compounds with an aromatic ring that is chemically bonded to one or additional hydrogenated substituents in the presence of corresponding functional derivatives. In honey, propolis, and royal jelly, phenolic compounds are commonly present as flavonoids . Various phenolic compounds contribute to the functional properties of bee products, including their antioxidant, antimicrobial, antiviral,anti-inflammatory, antifungal, woundhealing, andcardioprotective activities.

The nutrients found in honey

Health Benefits of Honey

Wound Management. Honey has traditionally been used to treat wounds, insect bites, burns, skin disorders, sores, and boils. Scientific documentation of the wound-healing capabilities of honey validates its efficacy as a promoter of wound repair and an antimicrobial agent. Honey promotes the activation of dormant plasminogen in the wound matrix, which results in the dynamic expression of the proteolytic enzyme. Plasmin causes blood clot retraction and fibrin destructions. It is an enzyme that breaks down fibrin clots with attached dead tissues in the wound bed.

Clinical evidence supporting the effectiveness, specificity, and sensitivity of honey in wound care indicates that the performance of conventional and modern wound care dressing is inferior to that using honey. Certain cases have shown that honey stimulates wound-healing properties even in infected wounds that do not respond to antiseptics or antibiotics and wounds that have been infected with antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA).

Honey also aids autolytic debridement and accelerates the growth of healthy granulated wound bed. Malodor is a general attribute of severe wounds caused by anaerobic bacterial species belonging to Bacteroides spp. And Peptostreptococcus spp. Malodourous compounds, such as ammonia, amines, and sulfur, are produced by bacteria during the metabolism of amino acids from putrefied serum and tissue proteins. These compounds are replaced by lactic acids as honey dispenses a substantial amount of glucose, a substrate metabolized by bacteria in preference to amino acids. The therapeutic effects observed after honey application include fast healing, wound cleansing, clearance of infection, tissue regeneration, minimized inflammation, and increased comfort during dressing due to lower extent of tissue adhesion.

Pediatric Care

Honey also controls skin damage near stomas, such as ileostomy and colostomy, by enhancing epithelialization of the afflicted skin surface. Honey has a beneficial effect on pediatric dermatitis caused by excessive use of napkins and diapers, eczema, and psoriasis. The effect of honey mixed with beeswax and olive oil was investigated on patients with psoriasis or atopic dermatitis condition. A clinical trial showed that a mixture containing honey was extremely well tolerated and caused significant improvements. Honey consists of various nitric oxide metabolites, which reduce the incidence of skin infection in psoriasis.

Diabetic Foot Ulcer (DFU)

Consumption of honey is a low-cost and effective therapy for the treatment of DFU. DFU is often complicated by microbial infections and slows the healing process. Apart from the infection, symptoms such as pain, swelling, and redness might not be present for diabetic peripheral neuropathy patients due to their reduced immune response, which further complicates the diagnosis. A review indicated that using honey for the treatment of venous ulcers yielded positive outcomes with good acceptance rates from the patients. Honey is used in wound management and is effective among patients with locally infected wounds, DFU, Charcot foot ulcerations, and complex comorbid conditions that have failed hospital management. In addition, there is excellent tolerability and minimal trauma to the wound bed in the presence of honey.

Gastrointestinal (GI) Disorder

Natural honey is composed of enzymes that facilitate the absorption of molecules, such as sugars and starch. The sugar molecules in honey are in a form that can be easily absorbed by the body. Honey also

provides some nutrients, such as minerals, phytochemicals, and flavonoids, that aid digestive processes in the body. Pure honey has bactericidal properties against pathogenic bacteria and enteropathogens, including Salmonella spp., Escherichia coli, Shigella spp., and many other Gramnegative species.

Biological Activities of Honey

  • Gastroprotective
  • Antiinflammatory
  • Wound healing
  • Cardioprotective
  • Antioxidant
  • Antidiabetic
  • Antibacterial
  • Anticancer

Oxidative Medicine and Cellular Longevity

The gastrointestinal tract (GIT) contains many important beneficial microbes. For example, Bifidobacteria is one of the microorganisms present primarily for the sustenance of a healthy GI system. It has been suggested that consuming foods rich in probiotics can increase the population of Bifidobacteria in the GIT. The biological activities and development of this bacteria are further enhanced in the presence of prebiotics. Studies have shown that natural honey contains high amount of prebiotics.

Some in vitro and in vivo experimental trials on honey have reported it as a prominent dietary supplement that hastens the growth of Lactobacillus and Bifidobacteria and catalyzes their probiotic potency in the GIT. Under in vitro conditions, prebiotic ingredients in honey such as inulin, oligofructose, and oligosaccharides promoted the increase in the numbers of Lactobacillus acidophilus and L. plantarum by 10–100 folds, which was beneficial for the intestinal microbiota.

Oral Health

Honey is useful for the treatment of many oral diseases, including periodontal disease, stomatitis, and

halitosis. In addition, it has also been applied for the prevention of dental plaque, gingivitis, mouth ulcers, and periodontitis. The antibacterial and anti-inflammatory properties of honey can stimulate the growth of granulation tissue, leading to the repair of damaged cells. Porphyromonas gingivalis is a Gram-negative bacteria that causes periodontitis. Honey exerts antimicrobial activity against this anaerobic bacteria and prevents periodontal disease. Inflammation of mucous membranes in the mouth (stomatitis) may induce redness and swelling of oral tissues and cause distinct and painful ulcers. Honey penetrates into the tissues very quickly and is effective against stomatitis.

Halitosis is an oral health condition that causes malodorous breath. Most of the odor in the oral cavity is caused by the activity of degrading microbes. A recent study has reported that honey consumption ameliorates halitosis  due to its strong antibacterial activity resulting from its methylglyoxal component.

Pharyngitis and Coughs

Pharyngitis, commonly known as sore throat, is an acute infection induced by Streptococcus spp. in the oropharynx and nasopharynx. In addition to streptococci, viruses, nonstreptococcal bacteria, fungi, and

irritants such as chemical pollutants may also cause sore throat. Manuka honey is effective for treating sore throat with its anti-inflammatory, antiviral, and antifungal properties. Honey coats the inner lining of the throat and destroys the harmful microbes while simultaneously soothing the throat.

A survey has demonstrated that honey is superior to other treatments for cough induced by upper respiratory infections, including dextromethorphan and diphenhydramine. The antioxidant and antimicrobial properties of honey aided in minimizing persistent cough and ameliorated sleep for both children and adults following honey intake (2.5 ml). A comparative study on children with different natural products reported that honey was found to be the widely used remedy for pneumonia 82.4%.

Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a mucosal infection caused by contents of abnormal gastric reflux into the esophagus and even the lungs. Symptoms of GERD include heartburn, inflammation, and acid regurgitation. Consumption of honey helps this condition by coating the esophagus and stomach lining, thus preventing the upward flow of food and gastric juice. Honey can further stimulate the tissues on the sphincter to assist in their regrowth and finally reduce the chances of acid reflux.

Dyspepsia, Gastritis, and Peptic Ulcer.

Dyspepsia is a chronic disease in which the GI organs, mainly the stomach and first part of the small intestine, function abnormally. It is a disease that causes epigastric pain, heartburn, bloating, and nausea as symptoms. Dyspepsia is the preliminary symptom of peptic ulcer which could eventually cause cancer. Gastritis refers to the irritation and inflammation of the lining of the stomach wall. Peptic ulcer denotes erosions or open painful ulcers on the lining of the stomach or duodenum. Honey have been identified as a potent inhibitor for gastritis and the peptic ulcer causing agent, Helicobacter pylori (H. pylori). Clinical surveys have shown that honey decreased the secretion of gastric acid and increased the healing effect. Thus, honey is taken as a dietary supplement for its antibacterial properties and protective effect. The high sugar content and low pH in honey are the results of glucose oxidative conversion to gluconic acid by glucose oxidase. This mechanism releases hydrogen peroxide, which functions as an antibacterial agent. Glucose oxidase also acts on fibroblasts and epithelial cell activators required for the healing of ulcers caused by H. pylori.


Gastroenteritis, known as stomach or gastric flu, causes inflammation of the digestive tract. This condition may be due to foodborne, waterborne, and person-to-person spread of infectious agents. The symptoms of gastroenteritis include dehydration, watery diarrhea, bloating, abdominal cramps, and nausea. There are many infectious agents, such as Salmonella, Shigella, and Clostridium, that can cause this condition. A clinical study by Abdulrahman, 2010, has reported the treatment of infantile gastroenteritis using honey. The study found that replacing the glucose in standard electrolyte oral rehydration solution (ORS) with honey reduced the recovery time of patients with gastroenteritis because the high sugar content in honey boosts electrolyte and water reabsorption in the gut.

Constipation and Diarrhea

Chronic constipation is a common and multifarious illness characterized by intolerable defecation (irregular stools and difficult stool passage). Difficult stool passage includes symptoms such as straining,

hard to expel stool, a sense of incomplete evacuation, hard or lumpy stools, and prolonged time to pass stool. Diarrhea is defined as a high frequency of bowel movements with watery stool. Honey has minimized the pathogenesis and duration of viral diarrhea compared to conventional antiviral therapy. In another case, people diagnosed with inflammatory bowel syndrome (IBS) experiencing severe diarrhea or constipation, bloating, and stomach discomfort was successfully treated with raw Manuka honey on an empty stomach.

Liver and Pancreatic Diseases

Honey helps to soothe pain, balance liver systems, and neutralize toxins. Complications in the liver system can be attributed to oxidative damage. Honey exhibits antioxidant activities that have a potential protective effect on the damaged liver. A study on paracetamol-induced liver damage rats showed that the antioxidant and hepatoprotective activity of honey minimized liver damage. Honey, which has a 1 : 1 ratio of fructose to glucose, may help to promote better blood sugar level, which is useful for those suffering from fatty liver disease since it provides adequate glycogen storage in liver cells.

Insufficient glycogen storage in the liver releases stress hormones that impair glucose metabolism over time. Impaired glucose metabolism leads to insulin resistance and is the main factor of fatty liver disease. Another study reported significant reduction in blood glucose levels after treatment with Tualang honey.

Metabolic and Cardiovascular Health

Natural wild honey exerts cardioprotective and therapeutic impacts against epinephrine-induced cardiac disorders and vasomotor dysfunctions. A harmonized relationship between radical scavenging activity and the total phenolic content of honey has been observed. Honey intake showed a significant

reduction in risk factors of metabolic and cardiovascular diseases. Honey exhibits cardioprotective effects such as vasodilation, balancing vascular homeostasis, and improvements in lipid profile. Flavonoids in honey improves coronary vasodilation, decreases the ability of platelets to form clots, prevents oxidation of low-density lipoproteins (LDL), increases high-density lipoproteins (HDL), and improves endothelial functions.

A study conducted to compare the metabolic response of honey has indicated its ameliorative effects against metabolic syndromes (MetS). MetS is denoted by hyperglycemia, hypertension, abdominal obesity, dyslipidemia, and intensified adaptability towards diabetes, kidney, and heart diseases. Polyphenols in honey reduce atherosclerotic lesions through the downregulation of inflammatory and angiogenic mechanisms. A clinical study conducted on patients with hyperlipidemia showed that honey decreased total cholesterol (TC) and noticeably prevented the rise in plasma glucose levels. Nitric oxide (NO) is a metabolite present in honey that also has cardioprotective functions.

Cancer and Oncogenesis

Breast Cancer

Imbalance in estrogen signaling pathways and propagating levels of estrogens have important roles in breast cancer growth and propagation. Treatments for breast cancer are associated with targeting the

estrogen receptor (ER) signaling pathway. Phytoestrogens are a subclass of phytochemicals with a common structure to the mammalian estrogen that enables them to bind to estrogen receptors. Several experimental studies have investigated the efficiency of honey in modulating the ER signaling


Another study has shown that honey has biphasic activity in MCF-7 cells. This biphasic activity of honey is represented by an antiestrogenic effect at lower concentrations and an estrogenic effect at higher concentrations, which is caused when phytoestrogens bind to estrogen receptors. Moreover, quercetin has been reported to induce apoptotic effects through ER α- and ER β-dependent mechanisms. On the other hand, cytotoxic activities of Tualang honey in human breast cancer cells were demonstrated by

elevated secretion of lactate dehydrogenase (LDH) and further illustrated the cytotoxic properties of honey. The study also showed that honey only exerts cytotoxic effects on breast cancer line and not on nonmalignant breast cells. Therefore, this indicates that Tualang honey shows highly specific and selective cytotoxic effects towards breast cancer cell lines and has a good potential as a chemotherapeutic agent.

Liver Cancer

The most common type of liver cancer is hepatocellular carcinoma (HCC). The antitumor effects of honey on liver cancer cells have been investigated in various experimental studies. Treatment of HepG2 cells with honey minimized the amount of nitric oxide (NO) levels in the cells and decreased the HepG2 cell number greatly. This increased the overall antioxidant profile of the cells. The survival of HepG2 cells is promoted by reactive oxygen species (ROS), and adequate levels of ROS trigger cell proliferation and differentiation.

Decreasing the amount of NO resulting from honey treatment supported this study. Thus, reduced ROS

and enhanced antioxidant efficacy inhibit cancerous cell proliferation and lowered the number of HepG2 cells. Another study done by Abdel Aziz et al. investigated the effects of honey on HepG2 cell lines. The report showed that honey exerted cytotoxic, antimetastatic, and antiangiogenic effects on HepG2 cells based on different concentrations.

Colorectal Cancer

Most colorectal cancers begin as a polyp, which generally starts on the inner lining of the colon or rectum and grows towards the center. Some polyps are not dangerous but some will eventually grow into adenomas and can eventually result in cancer. A study that investigated the chemopreventive effects of Gelam and Nenas monofloral honeys against colon cancer cell lines found that the honey inhibited proliferation of colon cancer cells. Hydrogen peroxide-induced inflammation in the colon cancer cells was used to examine the effect of honey. The results showed that honey curbed inflammation in the cancerous cells.

Another study was done to investigate the apoptotic effects of crude honey on colon cancer cell lines. The study confirmed the antiproliferative effect of honey in these cells. In addition, at high phenolic concentrations (such as those of quercetin and flavonoids), significant antiproliferative action against colon cancer cells was observed. The molecular mechanisms resulting in the antiproliferative and anticancer effects of honey include cell cycle arrest, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, reduction of inflammation, modulation of insulin signaling, and inhibition of angiogenesis in cancer cells. In addition, honey shows potential effects on cancer cell by modulating proteins, genes, and cytokines that promote cancer.

Several components of honey such as chrysin, quercetin, and kaempferol have been shown to arrest cell cycle at various phases such as G0/G1, G1, and G2/M in human melanoma, renal, cervical, hepatoma, colon, and esophageal adenocarcinoma cell lines. The mitochondrial pathway entails a chain of interactions between stimuli such as nutrients, physical stress, oxidative stress, and damage during

major cancer treatments including chemotherapy and radiotherapy. These stimuli cause several proteins located within the intermembrane space (IMS) of the mitochondria, such as cytochrome c, to be released, which eventually culminates in the death of the cell. Flavonoids in honey are effective in

activating the mitochondrial pathway and discharging proteins with potential cytotoxicity. Induction of mitochondrial outer membrane permeabilization (MOMP) is the most prevalent anticancer mechanism, which causes the leakage of proteins from the IMS and inevitably results in cell death.

Honey induces MOMP in cancer cell lines by decreasing the mitochondrial membrane potential. Honey has also been documented for amplifying the apoptotic effect of tamoxifen by intensified depolarization of the mitochondrial membrane. Flavonoid constituents of honey, such as quercetin, have been shown to trigger MOMP and lead to cancer cell death.

Fructose and high-fructose corn syrup

Fructose is ingested as one of two sources in our diet; as either free fructose or fructose bound to glucose (i.e. sucrose). Differences in uptake and metabolism of free fructose or fructose consumed as sucrose have been suggested; however, the magnitude of any differences between consumption of the two forms may be negligible when total fructose consumption (i.e. free fructose plus fructose consumed as sucrose) is considered. Fructose as a naturally occurring monosaccharide present in many

fruits and vegetables provides only modest amounts of free fructose to the host. Conversely, the soaring use of HFCS as a sweetener in soft drinks, baked goods and condiments is imparting a new challenge upon the intestinal environment in managing free fructose overloads.

HFCS is composed of a mixture of free fructose and glucose, typically 55% fructose to 45% glucose; however, these ratios frequently vary. Conservative estimates indicate 132–312 kcal person-1 d-1 is consumed as HFCS in the United States, where its widespread use in food manufacturing prevails compared with Western Europe, representing an increase in free fructose load of 158.5 kcal person-1 d-1 in 1978 to 228 kcal person-1 d-1 in 1998 (27,29). Furthermore, per capita estimates in the United States indicate HFCS consumption increased from 56.1 g d-1 between 1975 and 1980 to 73.4 g d-1 during the 1994–2005 period.

This substantial increase in fructose consumption has paralleled the increased incidence of obesity in the United States, suggesting its contribution to development of obesity. This assumption remains controversial as others have noted no unequivocal evidence linking free fructose consumption with metabolic disorders. The degree to which consumption of free fructose contributes to obesity may, however, be life stage dependent beginning with excessive consumption in childhood. For example, obese children ingest twice the amount of fructose in the form of sweets and sugar sweetened beverages in comparison to normal-weight children, a trend which if continued into adulthood could have implications for weight status.

Absorption of free fructose in the small intestine differs markedly from glucose and is primarily mediated by the GLUT5 transporter, with participation of GLUT2 also reported. Following food intake, apical GLUT2 and GLUT5 transporters alter their membrane insertion rate and activity in response to b-adrenergic agonists, gutderived hormones (e.g. glucagon-like peptides 1 and 2 ) and leptin levels. Fructose entering portal blood is extracted nearly 100% at first pass by the hepatic GLUT2 transporter where it is oxidized to CO2 with subsequent conversion to lactate and glucose. Lactate and glucose are then directed to de novo lipogenesis or converted to glycogen for storage.

Fructose has been reported as potentially orexigenic when administered centrally to mice, demonstrating an innate disruptive tendency in energy balance regulation. Fructose elicits no insulin secretion from b pancreatic cells and fails to stimulate satiety signalling from the brain. This effect may be mediated by a lack of functional GLUT5 in the brain despite its observation in various brain cells. This lack of insulin production results in insufficient plasma leptin levels needed to regulate further food intake.

Leptin is a pleiotropic hormone produced by many tissues, with serum levels correlating positively with body fat. Stomach-derived leptin has been demonstrated to regulate butyrate uptake by monocarboxylate transporter MCT-1 and SGLT-1 sodium-dependent glucose transport in the small intestine. Leptin also imparts a synergistic increase in GLUT5 mRNA expression in rats fed a high-fructose diet, resulting in a positive feedback loop of continual increased fructose absorption and subsequent leptin secretion. Furthermore, a concomitant decline in hepatic and intestinal fasting induced adipocyte factor (Fiaf) by fructose feeding was observed and not ameliorated by leptin administration.

Fiaf is a circulating inhibitor of lipoprotein lipase, an enzyme promoting triglyceride storage. Leptin may

further potentiate the lipogenic effect of fructose by induction of SREBP-1c and ACC-1, a hepatic lipogenic transcription factor and regulatory enzyme of fatty acid biosynthesis, respectively. Discovery of this intricate network of fructose-mediated leptin secretion, GLUT5 regulation and Fiaf suppression illustrates additional contributory mechanisms of free fructose consumption to lipogenesis with implications for development of hyperlipidaemia and metabolic disorders.

Non-nutritive sweeteners

Obesity is a major public health challenge that contributes to type 2 diabetes and cardiovascular disease. Evidence that sugar consumption is fuelling this epidemic has stimulated the increasing popularity of non-nutritive sweeteners, including aspartame, sucralose and stevioside. In 2008, more than 30% of Americans reported daily intake of non-nutritive sweeteners, and this proportion is increasing. Researchers have suggested that non-nutritive sweeteners may have adverse effects on glucose metabolism, gut microbiota and appetite control. Moreover, studies involving animals have reported that chronic exposure to non-nutritive sweeteners leads to increased food consumption, weight gain and adiposity.

The unfortunate position of the Academy of Nutrition and Dietetics is that non-nutritive sweeteners can help limit energy intake as a strategy to manage weight or blood glucose. However, consumption of non-nutritive sweeteners has been paradoxically associated with weight gain and incident obesity. A previous meta-analysis reported conflicting evidence: randomized controlled trials (RCTs) showed potential benefits (modest weight loss), whereas observational studies showed a small but significant association with increased body mass index (BMI). However, the review did not evaluate outcomes beyond body composition. Several studies involving more than 100 000 new participants and representing several new geographic settings have since been published.

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 reviews 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 studies 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, researchers found that consumption of nonnutritive sweeteners was associated with modest long-term weight gain in observational studies. The results also extend previous meta-analyses that showed higher risks of type 2 diabetes and hypertension with regular consumption of nonnutritive sweeteners.

The effects on the Gut

Identification of a single definitive cause or consequence of the commensal flora to obesity is unreasonable to assume. The multitude of host–microbe interactions elucidated over

with obesity. In conclusion, we suggest obesity treatment and prevention could be effectively achieved by promoting intestinal homeostasis through reintroduction of a balanced and diverse diet. The past 5 years provides strong evidence of a multifactorial network of parameters leading to development of obesity and associated metabolic disorders. It is widely accepted that dietary modulation of the gut microbiota is attainable, even desired for promoting certain ‘beneficial’ health effects. Conversely, the evidence presented here suggests we are unconsciously promoting a ‘westernized’ conditioning of the gut microbiota to reduced dietary diversity marked by increased consumption of fructose and sugar substitutes. The contribution of increased dietary fat to this process cannot be ignored but is not the focus of research, having received sufficient attention elsewhere. Continuous exposure to fructose and sugar substitutes may cause dysbiosis with loss of microbial genetic and phylogenic diversity, promoting evolution and maintenance of a Western gut microbiome. In turn adaptive metabolism generates additional energy sources for the host, which may facilitate aberrant host–microbe interactions leading to perturbed energy regulation and altered gut transit times with subsequent enhancement of dietary energy extraction. These differences in microbial composition and metabolic activity may ultimately be sensed by the innate and adaptive immune system leading to intestinal inflammation with later manifestation as endotoxemia. The combination of these processes can undoubtedly contribute to development of many metabolic disorders associated with obesity. In conclusion, we suggest obesity treatment and prevention could be effectively achieved by promoting intestinal homeostasis through reintroduction of a balanced and diverse diet.

Sucralose and the Gut

Studies have demonstrated that functional genes of the bacterial community are related to 16S rRNA marker genes, allowing the functional capacities of the gut microbiome to be surveyed using 16S rRNA gene sequencing. Using functional gene enrichment analysis, a number of genes related to bacterial pro-inflammatory mediators were shown to be significantly increased in the sucralose-treated gut microbiome, including genes involved in LPS synthesis, flagella protein synthesis, and fimbriae synthesis as well as bacterial toxins and drug resistance genes. LPS, flagella, and fimbriae are known PAMPs that can trigger pathological inflammation in the host, and various toxins produced by bacteria can induce toxicity in the host. LPS, a known endotoxin from the outer membrane of gram-negative bacteria, can initiate inflammatory events, such as the secretion of pro-inflammatory cytokines like interleukin-6ortumornecrosisfactor(TNF)-α. Flagella protein levels are low in a healthy gut, and high levels of flagella proteins have been shown to be associated with gut mucosal barrier breakdown and inflammation in previous studies. Fimbriae play an important role in bacterial adhesion to and invasion of epithelial cells and are known virulence factors.

Additionally, multidrug resistance genes were increased in the sucralose treated gut microbiome, and the increase in multidrug resistance genes and/or multidrug-resistant bacteria may lead to a more hostile gut environment. These data indicate that 6 months of sucralose consumption increased the pro-inflammatory products of the gut microbiome and its ability to potentially induce systemic inflammation.

Proposed functional link between sucralose-induced gut microbiota alterations and host inflammation. Sucralose perturbs the gut microbiome and its metabolic functions, inducing the enrichment of bacterial pro-inflammatory mediators, and disrupting metabolites involved in inflammation regulation. Together, these consequences may contribute to the induction of liver inflammation in the host.

Sucralose Lights up tumours in an MRI machine

Researchers evaluated the use of the inexpensive, non-caloric sweetener sucralose as an MRI contrast agent based on chemical exchange to image tumors in vivo. In the normal rat brain, no change in the sucCEST contrast was observed following intravenous injection of sucralose, suggesting that sucralose does not cross the BBB and therefore can be used to image BBB disruption. Increased sucCEST contrast was observed in the tumor region, which is presumably due to the accumulation of sucralose in the extravascular extracellular space (EES) of the tumor. Te brain tumor compromises the BBB and allows sucralose to enter the tumor EES.

SucCEST sensitivity of 1.1% per mM sucralose translates to a ~1000-fold higher sensitivity than the direct detection with MRS, enabling the detection of millimolar concentrations.

Recently, d-glucose has been used as a CEST MRI contrast agent to image cancers (glucoCEST). However, the interpretation of glucoCEST results might be intricate as the d-glucose is readily metabolized by both tumors and healthy tissue. Glucose analogues such as 2-deoxy-d-glucose (2-DG) and 2-fuoro-deoxy-d-glucose (FDG) were also shown to have higher CEST efect compared to glucose. Tis may be due to rapid conversion of glucose into lactate by the tumors whereas 2-DG and FDG are not metabolized. As tumors are highly glycolytic, the injected glucose or pyruvate rapidly metabolize into lactate. Using the recently developed LATEST method to measure CEST contrast from lactate, it may be possible to map the glycolytic behavior of tumors as well as probe the kinetics of LDH activity in tumor. Another glucose derivative, 3-O-methyl-glucose (3-OMG) has recently been used as an MRI contrast agent to image cancer in orthotopic xenograft of a mammary adenocarcinoma model . 3-OMG is taken up rapidly and preferentially by the tumor cells and stored. Tis contrasts with 2-DG and FDG, which undergo phosphorylation. Studies have shown that 3-OMG diffuses into normal brain tissu, though, limiting its use in the brain tumor imaging.

As sucralose is not metabolized in the body, the tumor sucCEST kinetics may be governed by the wash-in/wash-out of sucralose. Although we demonstrated the sucCEST in the brain tumor model, the method can potentially be useful to image other types of tumors and to monitor anti-tumor drug efficacy. Sucralose phantom studies showed the highest CEST efect for saturation parameters of 7 µT and 3 s duration in vitro.

SucCEST map of a rat brain glioma. a sucCEST contrast map from a rat with glioma shows increased contrast in tumor region following intravenous injection of sucralose with the sucCEST contrast peaking at 30 min post injection. b The kinetics showing the average percentage change from the baseline in the sucCEST contrast from tumor rats at different time points, which peaks ~30 min post end of infusion. c MTRasym curves generated from tumor ROI at baseline and post 30 min following the end of sucralose infusion show increased contrast at 1 ppm. d The normal brain, no signal change at 1 ppm post 30 min was observed in the MTRasym curve.

This inexpensive, non-caloric sweetener can be readily used for routine examination of various tumors on ultrahigh field MRI scanners based on contrast generated from the chemical exchange of its labile hydroxyl protons with water. In addition, it can potentially be used to study BBB derangements, noninvasively. This preliminary study paves the way for the development of sucralose and other sucrose derivatives as MRI contrast agents for a variety of human clinical imaging applications as well as to monitor therapeutic response.

Aspartame and your Kidneys and Brain

Oxidative stress is characterized by increased level of pro-oxidants such as reactive oxygen species and reactive nitrogen species or decreased level of antioxidants that could lead to cell dysfunction and degradation. It seems that the decreased activity of antioxidant enzymes in aspartame-fed animals might be due to methanol production or some other metabolites. Once ingested, aspartame is metabolized to aspartic acid, phenylalanine, and methanol in the ratio of 50:40:10, respectively, and also a small amount of aspartyl phenylalanine diketopiperazine, especially during its heating.

Methanol further oxidized to formaldehyde, which is accompanied by the formation of superoxide anion and hydrogen peroxide in the kidney and some other organs like liver and brain. The other metabolite, diketopiperazine, seems to be a carcinogen.

Researchers have reported a significant increase of plasma methanol level and free radical production after aspartame administration. Moreover, other scientists reported a 61-year-old man with suspected methanol poisoning transferred to the Regional Center of Clinical Toxicology, the laboratory tests of whom showed metabolic respiratory acidosis, and investigations revealed that a few days prior to the hospitalization the patient was drinking a great amount of fruit juices sweetened with aspartame and milk (more than 12 liters per day).

They concluded that excessive consumption of aspartame might lead to methanol poisoning in this patient. It seems that humans are more sensitive to the toxic effects of methanol because of the slow methanol oxidation and low liver folate content compared to the other animals, such as rodents.

In a recent study, Saleh reported a significant decrease in glutathione level and the activity of glutathione peroxidase and catalase in the kidney tissue of aspartame-fed rats, which was significantly reversed during the administration of folic acid and N-acetyl cysteine. Similarly, Finamor and associates showed the protective effect of N-acetyl cysteine against the oxidative damage of the brain in long-term aspartame-fed rats.

Overall, most of the current data on the nephrotoxic effect of aspartame are based on the results of experimental studies and such adverse effects have not been assessed in humans. Moreover, one limitation of those animal studies was oral treatment with a high dose of aspartame, consumption of which seems to be unusual by humans. However, future epidemiological studies and clinical trials are needed to investigate the adverse effects of long-term consumption of aspartame at the acceptable daily intake.

In conclusion, based on these observations long-term or high-dose consumption of aspartame may lead to a dose-dependent increase in free radical production and some adverse health effects, including kidney injury, especially in some conditions such as diabetes mellitus, older ages, and intense and prolonged exercise with innately increased production of free radicals. Therefore, consumers should be aware of the potential side effects of aspartame, albeit there is not a conclusive clinical data about those adverse effects.

Aspartame and Saccharin and Your Liver

An interesting study was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure.

Sweeteners in Breast Milk

A study was undertaken to determine sucralose and acesulfame-K pharmacokinetics in breast milk. Following maternal ingestion of a diet soda. Thirty-four exclusively breastfeeding women (14 normal eight, 20 obese)  consumed twelve ounces of Diet Rite Cola™, sweetened with 68 mg sucralose and 41 mg  acesulfame-potassium, prior to a standardized breakfast meal. Habitual LCS intake was  assessed via a diet questionnaire. Breast milk was collected from the same breast prior to beverage ingestion and hourly for six hours.

Due to one mother having extremely high concentrations, peak sucralose and  acesulfame-potassium concentrations following ingestion of diet soda ranged from 4.0 to 7,387.9 ng/mL (median peak 8.1 ng/mL) and 299.0 – 4764.2 ng/mL (median peak 945.3  ng/mL), respectively.

The researchers concluded that Ace-K and sucralose transfer into breast milk following ingestion of a diet soda. Future research should measure concentrations after repeated exposure and determine whether chronic ingestion of sucralose and acesulfame-potassium via the breast milk has clinically relevant health consequences.

Ace-K Makes You Fat

Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.


Stevia glycosides, extracted from the leaves of the plant Stevia rebaudiana Bertoni, display an amazing high degree of sweetness. As processed plant products, they are considered as excellent bio-alternatives for sucrose and artificial sweeteners. Being noncaloric and having beneficial properties for human health, they are the subject of an increasing number of studies for applications in food and pharmacy. However, one of the main obstacles for the successful commercialization of Stevia sweeteners, especially in food, is their slight bitter aftertaste and astringency. These undesirable properties may be reduced or eliminated by modifying the carbohydrate moieties of the steviol glycosides. A promising procedure is to subject steviol glycosides to enzymatic glycosylation, thereby introducing additional monosaccharide residues into the molecules. Depending on the number and positions of the monosaccharide units, the taste quality and sweetness potency of the compounds will vary.

Monk Fruit – One of the good guys.

What are the benefits of monk fruit?


  1. Sweeteners made with monk fruit don’t impact blood sugar levels.
  2. With zero calories, monk fruit sweeteners are a good option for people watching their weight.
  3. Unlike some artificial sweeteners, there’s no evidence to date showing that monk fruit has negative side effects.

    There are several other pros to monk fruit sweeteners:

    • They’re available in liquid, granule, and powder forms.
    • They’re safe for children, pregnant women, and breast-feeding women.
    • According to a 2009 study, monk fruit gets its sweetness from antioxidant mogrosides. The study found monk fruit extract has the potential to be a low-glycemic natural sweetener.
    • 2013 studyconcluded mogrosides may help reduce oxidative stress. Oxidative stress may lead to disease. Although it’s unclear how specific monk fruit sweeteners come into play, the study shows monk fruit’s potential.


      What are the disadvantages of monk fruit?


      1. Monk fruit is difficult to grow and expensive to import.
      2. Monk fruit sweeteners are harder to find than other sweeteners.
      3. Not everyone is a fan of monk fruit’s fruity taste. Some people report an unpleasant aftertaste.

      Other cons to monk fruit sweeteners include:

      • Some monk fruit sweeteners contain other sweeteners such as dextrose. Depending on how the ingredients are processed, this may make the end product less natural. This may also impact its nutritional profile.
      • Mogrosides may stimulate insulin secretion. This may not be helpful for people whose pancreas is already overworking to make insulin.

        The Take Home Message

        I guess the best message is not to have any sweeteners, including of course sugars. But, back to reality and some sweeteners are better than others. Stevia and Monk fruit is good stuff. Erythritol is good also but cost can be prohibitive.

        There are problems taking them as a weight loss agent because the research suggests they should be avoided if you are trying to lose weight because they spike insulin when taken and reduce fat burning.

        We can’t avoid the increases in vascular disease when talking about these sweeteners, nor can we ignore studies suggesting cancer may be an issue also.

        If you can’t eliminate them from your diet, just reduce the amount you consume to a minimal amount to reduce harm.



        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

        Visweswara Rao Pasupuleti,1,2 Lakhsmi Sammugam,2 Nagesvari Ramesh,2 and Siew Hua Gan3 Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 1259510, 21 pages

        Fructose impacts on gut microbiota and obesity A. N. Payne et al. Obesity reviews (2012)

        Fructose impacts on gut microbiota and obesity A. N. Payne et al. Obesity reviews (2012)

        Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Meghan B. Azad PhD, Ahmed M. Abou-Setta MD PhD, Bhupendrasinh F. Chauhan MPharm PhD, Rasheda Rabbani PhD, Justin Lys MD, Leslie Copstein MD, Amrinder Mann MD, Maya M. Jeyaraman MD PhD, Ashleigh E. Reid MPAS, Michelle Fiander MLIS, Dylan S. MacKay PhD, Jon McGavock PhD, Brandy Wicklow MD MSc, Ryan Zarychanski MD MSc. CMAJ 2017 July 17;189:E929-39.

        Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Meghan B. Azad PhD, Ahmed M. Abou-Setta MD PhD, Bhupendrasinh F. Chauhan MPharm PhD, Rasheda Rabbani PhD, Justin Lys MD, Leslie Copstein MD, Amrinder Mann MD, Maya M. Jeyaraman MD PhD, Ashleigh E. Reid MPAS, Michelle Fiander MLIS, Dylan S. MacKay PhD, Jon McGavock PhD, Brandy Wicklow MD MSc, Ryan Zarychanski MD MSc. CMAJ 2017 July 17;189:E929-39.

        Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Meghan B. Azad PhD, Ahmed M. Abou-Setta MD PhD, Bhupendrasinh F. Chauhan MPharm PhD, Rasheda Rabbani PhD, Justin Lys MD, Leslie Copstein MD, Amrinder Mann MD, Maya M. Jeyaraman MD PhD, Ashleigh E. Reid MPAS, Michelle Fiander MLIS, Dylan S. MacKay PhD, Jon McGavock PhD, Brandy Wicklow MD MSc, Ryan Zarychanski MD MSc. CMAJ 2017 July 17;189:E929-39.

        Fructose impacts on gut microbiota and obesity A. N. Payne et al. Obesity reviews (2012)

        Bian X, Chi L, Gao B, Tu P, Ru H and Lu K (2017) Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front. Physiol. 8:487.

        Bian X, Chi L, Gao B, Tu P, Ru H and Lu K (2017) Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front. Physiol. 8:487.

        Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection Puneet Bagga1†, Mohammad Haris2†, Kevin D’Aquilla1 , Neil E. Wilson1 , Francesco M. Marincola2 , Mitchell D. Schnall1 , Hari Hariharan1  and Ravinder Reddy1* Bagga et al. J Transl Med (2017) 15:119

        Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection Puneet Bagga1†, Mohammad Haris2†, Kevin D’Aquilla1 , Neil E. Wilson1 , Francesco M. Marincola2 , Mitchell D. Schnall1 , Hari Hariharan1  and Ravinder Reddy1* Bagga et al. J Transl Med (2017) 15:119

        Nephrotoxic Effect of Aspartame as an Artificial Sweetener-A Brief Review Mohammad Reza Ardalan,1 Hadi Tabibi,2 Vahideh Ebrahimzadeh Attari,1 Aida Malek Mahdavi3 Iranian Journal of Kidney Diseases | Volume 11 | Number 5 | September 2017

        Int J Immunopathol Pharmacol. 2015 Jun;28(2):247-55. Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach. Alkafafy Mel-S1, Ibrahim ZS2, Ahmed MM3, El-Shazly SA4.

        J Pediatr Gastroenterol Nutr. 2017 Oct 27. Pharmacokinetics of Sucralose and Acesulfame-Potassium in Breast Milk Following Ingestion of Diet Soda. Rother KI1, Sylvetsky AC, Walter PJ, Garraffo HM, Fields DA.

        Bian X, Chi L, Gao B, Tu P, Ru H, Lu K (2017) The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoSONE 12(6): e0178426

        Adv Carbohydr Chem Biochem. 2016;73:1-72. Stevia Glycosides: Chemical and Enzymatic Modifications of Their Carbohydrate Moieties to Improve the Sweet-Tasting Quality. Gerwig GJ1, Te Poele EM1, Dijkhuizen L1, Kamerling JP1.