Inside The Box with Dr Andy Gray | Are Complementary Medicines Effectively Regulated in South Africa?

#InsideTheBox is a column by Dr Andy Gray, a pharmaceutical sciences expert at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. (Photo: Supplied)

By Dr Andy Gray for Spotlight

The regulation of complementary and alternative medicines in South Africa has been hotly contested in recent decades, including in court rooms. In his latest column for Spotlight, Dr Andy Gray unpacks the legal background and the current state of this still unfolding regulatory saga.

Multivitamin and mineral supplements are commonly found in many South African retail outlets, from pharmacies to health shops and supermarkets. Some outlets will stock a wider range of medicines, perhaps on shelves marked as “complementary”, or among other non-prescription medicines available for self-service.

Are these medicines regulated in the same way as other medicines, including those available on prescription?

The concept of a “call-up notice”

When South Africa’s medicines legislation was first passed in 1965, there were already many medicines on the local market which had not been assessed for safety, efficacy or quality. As all such medicines could not be immediately “called up” for registration, a stepwise approach had to be followed.

Between 1967 and the mid-1980s, medicines were identified for registration by pharmacological classification. The remnant of that approach is still evident in section 14(1) and (2): of the Medicines and Related Substances Act, 1965:

(1) Save as provided in this section or sections 21 and 22A, no person shall sell any medicine, … which is subject to registration by virtue of a declaration published in terms of subsection (2) unless it is registered.

(2) (a) The Authority may from time to time determine that a medicine, …, or class or category of medicine, … or part of any class or category of medicine, … mentioned in the declaration, shall be subject to registration in terms of this Act.

(b) Any such declaration may also relate only to medicines, … which were available for sale in the Republic immediately prior to the date on which it comes into operation in terms of paragraph (c) or only to medicines, … which were not then so available.

The declaration that a category or class of medicine is subject to registration is referred to colloquially as a “call-up notice”. A notice could be applied to those medicines already marketed, or only to those not yet marketed. Medicines which were already marketed but exempted from a full registration process were then regulated as “old medicines”. They are still subject to control according to their scheduling status and their production still needs to be in accordance with Good Manufacturing Practice. In time, new brands of some of the “old medicines” have been registered.

By the mid-1980s, the process of working through the pharmacological classifications was concluded. Thereafter, every new medicine would need to be registered before being marketed. In other words, a manufacturer or importer would need to provide sufficient evidence of the medicine’s safety, efficacy and quality to justify registration.

However, an important exception was created in 1986, which exempted homeopathic medicines from the full registration process. Two important restrictions were included. Firstly, no medical claims could be made for the medicine. Secondly, the following wording was to be included on the label of such medicine: “Homeopathic Medicine” and “WARNING: Use only as directed by a medical practitioner, pharmacist or homeopath”. The provision applied to homeopathic mother substances and so-called “minute-dose forms” made in accordance with homeopathic principles.

Broadening the scope of complementary medicines

Homeopaths are one of several complementary and traditional health professions regulated by the Allied Health Professions Council of South Africa. Medicines legislation has been amended to accommodate this wider range of complementary and traditional medicines.

A separate South African Health Products Regulatory Authority (SAHPRA) web site is dedicated to what are termed Category D medicines, also known as complementary medicines.

The General Regulations issued in terms of the Medicines Act includes a definition of complementary medicines which has two components: health supplements and medicines used in accordance with a “discipline as determined by the Authority”. The pharmacological classifications listed in Annexures 1 (human) and 2 (veterinary) medicines list the “disciplines” as Aromatherapy, Homeopathy, Phytotherapy, Traditional Chinese Medicine, Unani Medicine, Western Herbal Medicine, Combination Products and Other Herbal. The Annexures also list the types of health supplements, including amino acids, mineral, probiotics and vitamins. Two elements are important here – the nature of the substance included in the complementary medicine and the claims made in relation to that medicine.

Since 2013, the intention has been to progressively bring all complementary medicines under effective regulation, using a risk-based approach to identify those requiring registration and full assessment of safety, efficacy and quality data. The first pharmacological classifications identified were those claiming antiviral properties, and those intended to treat diabetes, cardiac conditions and cancer. However, no complementary medicines have yet been registered and the initial “call-up notices” have been repealed.

Like much of South Africa’s medicines regulatory space, this process has been affected by litigation. A challenge of the complementary medicines regulatory scheme by the Alliance of Natural Health Products (South Africa) was finally decided by the Supreme Court of Appeal in 2022. The court confirmed the finding that SAHPRA should have no regulatory power over substances and preparations that did not meet the definition of a medicine. A preparation that seeks to supplement a diet or provide a nutritional benefit is not a medicine, but a foodstuff. Draft amendments to the 2017 General Regulations, informed by the court judgment, were published for comment in March 2023, but have yet to be issued in final form.

Not a total lack of regulation

The hiatus in finalising regulations does not mean, however, that there is no regulatory control over complementary or Category D medicines. The initial “roadmap” outlined in the 2013 regulations has been replaced by a series of guidelines. The progressive, developmental approach to the regulation of complementary medicines remains in place, albeit delayed and as yet incomplete.

The overall roadmap was updated in 2021. All manufacturers, wholesalers or distributors of complementary medicines are required to be licensed by SAHPRA, but this process relies on an applicant’s “attestation of compliance with minimum requirements at the time of application and the payment of the required licence application, and desktop evaluation fees”, rather than the full Good Manufacturing Practice inspection applied to manufacturers of other medicines. However, SAHPRA reserves the right to conduct inspections where warranted. A similar approach is applied to the regulation of medical devices and diagnostic tests.

In the meantime, while no complementary or alternative medicines have been registered by SAHPRA, there is relatively strict regulation of what companies can say about the unregistered complementary medicines that they market in South Africa.

As with the 1986 exclusion for homeopathic products, all category D products which have not been registered have to include the following statement on the label: “This unregistered medicine has not been evaluated by the SAHPRA for its quality, safety or intended use”. The guideline also distinguishes between low risk and high-risk claims, in either labelling or advertising. Low risk claims are those for general health enhancement without any reference to specific diseases; health maintenance; or the relief of minor symptoms (not related to a disease or disorder).

The guideline is specific about a widely used wording: “Unregistered complementary medicines making use of the terms “Clinically proven” or any similar expression … shall also be considered to be HIGH RISK and may be subject to individual call-up in terms of section 14(2) of the Medicines Act.” Examples of acceptable low risk claims are provided, such as “Helps enhance/promote joint health”. Further guidance on the evidence to be relied upon for low risk and high-risk claims has been provided for the discipline-specific complementary medicines.

Manufacturers and importers of health supplements are only allowed to make low risk claims, and the relevant guideline provides Annexures (from Annexure A to O), showing the allowable levels and claims for each type of supplement. For example, a single component vitamin B3 (nicotinamide) product sold for adults may not contain more than 500mg per dose, and can only make a claim of “Helps to metabolise carbohydrates, fats and proteins”, “Contributes to normal growth and development” or “A factor in the maintenance of good health”.

A key document is the current guideline on the regulation of discipline-specific complementary medicines. An additional guideline was updated in 2022, which provides guidance on caffeine, menthol, camphor and cannabidiol. Low-dose cannabidiol can be sold as either a discipline-specific complementary medicine or a health supplement. At a dose not exceeding 20mg per day or 600mg per pack, it can be sold as a Schedule 0 product.

As no complementary medicines have yet been registered, none have as yet been specifically included in any of the Schedules, and they are therefore assumed to be controlled as Schedule 0 products, which can be sold in any retail outlet. One exception would be any injectable product, as those are automatically included in Schedule 3 and are prescription-only.

Important sources of information

The SAHPRA complementary medicines website provides a crucial resource which can be accessed by the public. The list of licensed complementary medicines manufacturers, importers and exporters is accessible here. There are currently 117 entries on the list. Each entry also provides a list of the products provided by that licensed entity, with details of ingredients, recommended doses and intended uses, whether discipline-specific or health supplement. The entire database is also searchable.

The site also enables anyone to lodge a complaint about a complementary medicine, including anonymous complaints.

Gaps in the system

While some progress has been made, the regulatory scheme for complementary medicines remains incomplete. Apart from finalising the regulations after the court challenge, a risk-based “call-up” process still needs to commence. Moving from an attestation process to confirmation that every manufacturer has met current Good Manufacturing Practice standards is still necessary.

Currently, the proprietary (brand) names used for complementary medicines are not pre-approved by SAHPRA, and many are in contravention of the naming guidelines applied to other medicines.

Effective oversight of advertising and marketing practices remains elusive, not only in respect of complementary medicines.

The dictum traditionally applied to consumer goods of “let the buyer beware” (in Latin, “caveat emptor”) is no longer considered appropriate. The Consumer Protection Act, 2008 seeks to protect the public against unsafe products and unfair marketing. Medicines are treated as a special category of goods, deserving closer regulatory control. The remaining gaps in the medicines regulatory system need to be plugged. One very particular gap, which has never been adequately addressed, is the regulation of African traditional medicines, which are not currently captured in the definition of Category D medicines.

 – Gray is a Senior Lecturer at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice.

Disclosure: Gray serves on three technical advisory committees at the South African Health Products Regulatory Authority.

*This column was published by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.

How Paediatric Radiology Gives Answers when Children Cannot

Children are NOT small adults. They experience and express illness and injury very differently from adults. Which is why paediatric diagnostic imaging is a highly specialised field of medical imaging and is specifically designed for children, from birth to adolescence.

Dr Ebrahim Banderker, a paediatric radiologist at Red Cross War Memorial Children’s Hospital (RXCH), explains why children need a different approach to imaging and the role of radiology in children. He also talks about the success of a public-private initiative with SCP Radiology where he is a consulting radiologist.

Why is paediatric imaging so important?

Children are often unable to, or struggle to describe the nature of their discomfort, pain or symptoms clearly. Imaging helps doctors understand what is happening inside the body, when language and understanding are limited.

When we diagnose early, we are often preventing future pain, disability or developmental issues as well as reducing the anxiety of the family. 

What should parents know or understand about paediatric radiology?

Paediatric imaging is designed with the needs, safety and the specific conditions of children in mind. It is a tool for clarity, reassurance and early care. Our goal is to care for the child in their imaging journey and provide their doctors and families with clear answers they can trust.

How is paediatric radiology different from adult radiology?

  • The choice of the method of imaging is primarily based on how safe it is. The effects of radiation from X-rays and CT scans have a greater risk for a child than an adult – so ultrasound and MRI are preferred where possible.
  • Children are often afraid, unsettled because of pain and anxiety and may require sedation or anaesthesia to make them comfortable during the imaging process.
  • Paediatric imaging equipment, anaesthetic apparatus, monitoring and emergency equipment have to be adapted to children of different ages.

Do paediatric radiologist work directly with children and their parents?

Paediatric radiologists interact with the child and their caregivers far more often than adult radiologists interact with their patients. It is one of the most rewarding aspects of our work. Parents are generally more involved and can help the radiologist by confirming the history and symptoms. The radiologist in turn can reduce parent anxiety, explain the procedure and obtain consent where needed.

Please can you talk about radiation and safety in children – we know that one of the issues both parents and other adults have is safety and radiation?

Children have rapidly developing cells and tissues, often tightly packed together in small bodies and are considered to be 10-15 times more sensitive to radiation.  

The guiding principle of all radiation safety is ‘ALARA,’ which stands for ‘As Low As Reasonably Achievable’ or as we say, ‘when benefit clearly outweighs the risk.’  Ultrasound and MRI do not use radiation and these should be used where possible.

What injuries are commonly seen in children that require imaging?

Common injuries include those from motor vehicle accidents and particularly pedestrian accidents, fractures from falls or playing sport and unfortunately, increasingly from child abuse which is sometimes first identified by the radiologist.

Children’s bones are different from adults and have areas where the bone is still growing. These are called growth plates. Injuries to the growth plates require special care because they can affect how a bone develops and this impacts the overall growth of the child. 

Outside of injuries, paediatric imaging also looks at chest infections, abdominal pain, appendicitis, urinary tract problems and hip development in infants. Brain imaging may be used for seizures, headaches or developmental concerns. In essence, imaging can help us rule out serious causes quickly, which brings enormous reassurance to families.

Even for adults, radiology can be stressful and frightening – for children it must be worse.  How are children supported during scans?

Radiographers and radiologists are trained to work gently and calmly with children and parents are encouraged to be involved and ask questions. For example, when a child needs to be sedated for an MRI, the parent will stay with them until they are asleep. When children feel safe, the scan is quicker, easier and more accurate. The team ensures the child is warm and comfortable and the environment is child friendly with toys and reading material to distract patients and to keep them happy and engaged.

What developments in paediatric radiology do you feel are the most important – especially over the 5 years?

  • Digital radiography allows for digital manipulation of images improving image quality and accuracy. Retakes are reduced so there is less radiation involved
  • Ultrasound machines have improved in-depth visualisation of body parts, disease processes and blood vessels
  • CT scanners are faster and offer lower radiation dose options. There are scanners which can scan the entire body of a child in less than a second.  There is not even time to wriggle…
  • MRI imaging is developing at a galloping pace with faster scanning techniques and finer image detail
  • Functional MRI and the ability to do tissue sampling in cancer imaging, is opening many exciting new avenues. 

The scope of interventional radiology techniques (treating not just diagnosing) is expanding rapidly to make less invasive treatment possible, with less complications for patients and much shorter recovery times. Paediatric radiology increasingly includes minimally invasive procedures (image-guided drainages, biopsies, nephrostomies, angiography), which can shorten hospital stays and reduce surgical burden. 

Cosmetic Procedure Addiction Risk May Link to Social Media and Body Image

Photo by Freestocks on Unsplash

As cosmetic procedures surge worldwide and beauty content increasingly dominates social media platforms, a new study from the Hebrew University of Jerusalem, suggests that for some women, cosmetic treatments may begin to resemble compulsive or addiction-like behaviour. The study, led by Dr Vera Skvirsky alongside Dr Uri Lifshin, Dr Dvora Shmulewitz, and Prof Mario Mikulincer from the Department of Psychology at Hebrew University of Jerusalem and the Israel Center for Addiction and Mental Health (ICAMH), examined what the researchers describe as “addictive cosmetic procedures use,” or ACPU, among women.

Published in the Journal of Health Psychology, the study surveyed 1614 women between the ages of 25 and 71, making it one of the larger investigations to date into the psychological patterns associated with repeated cosmetic treatments. The findings point to a phenomenon that researchers say deserves greater attention from both clinicians and the public. Among women who had undergone cosmetic procedures, 20% met the threshold for moderate to severe risk of addictive cosmetic procedure use during their lifetime.

More than 15% reported symptoms that were active within the past year.

Across the full sample, nearly 9% of women showed moderate to severe signs of problematic cosmetic procedure use. The researchers adapted an assessment tool originally based on the Diagnostic and Statistical Manual of Mental Disorders criteria for substance-related disorders. Participants were asked questions typically associated with addiction, including whether they had unsuccessfully tried to stop undergoing cosmetic procedures, felt compelled to continue despite negative consequences, or experienced cravings related to treatments.

While previous research has linked cosmetic procedures to body image concerns and body dysmorphic disorder, this study goes further by examining whether repeated cosmetic treatments can, in some cases, resemble a behavioural addiction. Unlike earlier studies, which often focused on patients at cosmetic clinics, this research surveyed more than 1600 women from the general population and found that addiction-like patterns were most strongly associated with the combination of low body esteem and problematic social media use.

While cosmetic procedures are often associated with confidence and self-expression, the researchers found that repeated engagement may also intersect with vulnerabilities tied to body image and digital behaviour. Women with lower body esteem were significantly more likely to report addictive patterns of cosmetic procedure use, particularly when paired with high levels of problematic social media use. Participants who reported problematic or excessive social media behaviour were especially vulnerable if they also struggled with dissatisfaction about their appearance.

The researchers also observed smaller associations between addictive cosmetic procedure use and lower feminist attitudes, lower attachment security, and more negative attitudes toward aging, though those relationships were less consistent once multiple factors were analysed together.

The findings arrive amid a sharp global increase in cosmetic procedures. According to international estimates cited in the paper, cosmetic interventions worldwide rose by roughly 40% between 2019 and 2023.

The researchers stressed that the study does not argue cosmetic procedures are inherently harmful. Rather, they say the results suggest that in some cases, repeated engagement may take on characteristics similar to behavioral addictions already recognized in mental health research.

“Cosmetic procedures have become deeply normalised in many societies, and for many people they may be a positive experience,” said the researchers. “But our findings suggest that for a meaningful minority, the behaviour may begin to resemble other compulsive patterns we see in addiction research, especially when low body esteem and problematic social media use are involved.”

The researchers cautioned that the study was cross-sectional, meaning it cannot determine cause and effect. It remains unclear whether problematic social media use contributes to addictive cosmetic behaviour, whether cosmetic procedures themselves influence body image and online engagement, or whether other psychological factors drive both.

Source: Hebrew University of Jerusalem

Outdated Ideas About Antibiotics are Common, Study Finds

Photo by Towfiqu barbhuiya

“Always finish your antibiotics” is no longer considered medical best practice for all conditions. This may come as a surprise for many patients.

A new study has found that almost 90% of Americans believe that it’s always best to take the full course of antibiotics, even when you feel better – consistent with long-running but now outdated health campaigns. The reality is more complicated. Sometimes shorter courses are safer, and sometimes longer courses are best.

The survey demonstrates a need for better communication between doctors and patients about what’s healthiest.

“Historically, there was very strong guidance by major health organisations and clinicians that you must always finish the course,” says Alistair Thorpe, PhD, research assistant professor of population health sciences at University of Utah Health and first author on the study. “Now, we’re seeing a growing body of evidence saying that that is not always the case. And oftentimes, shorter durations of antibiotics are as effective and safe as longer alternatives.”

The results are published in Open Forum Infectious Diseases.

A complex reality

The research team surveyed 1475 people across the country on their attitudes about antibiotic course length. They asked participants whether they’d feel more comfortable taking a three- to five-day course of antibiotics if they had pneumonia, as is recommended by current guidelines, or if they’d prefer an antibiotic course of a week or more, which is recommended by outdated guidelines. While shorter courses of antibiotics are as effective and safer for pneumonia than longer ones, about 60% of people said they’d rather take the longer course. 

One of the main reasons people gave for preferring longer antibiotic courses was that they had been told to “always finish their antibiotic course” – 88% of respondents had heard of, and agreed with, this common mantra. Most had been told this by their clinician, and many had also heard it via a public health campaign.

A strong body of scientific evidence shows that, for many common infections, shorter courses of antibiotics work as well as longer courses and are less likely to cause side effects. Still, there are some cases, like tuberculosis, where longer courses are most effective. 

The study authors suggest that doctors and public health campaigns use several evidence-informed strategies to better communicate the complex reality of antibiotic course length – for instance, avoiding overly simplistic claims that either shorter or longer courses are universally better, and acknowledging that as scientific evidence accumulates over time, health recommendations can change. 

To patients who have been prescribed antibiotics, Thorpe recommends having an open conversation with your doctor about the appropriate course length and adherence plan to get health advice that’s specific to your situation.  

“Discuss with your clinician what the right duration is for you and when the right time is to stop your course,” Thorpe says. “Getting advice directly from a clinician on a one-to-one basis about what is most appropriate for you in that situation is the right way to go.”

Thorpe emphasises that the changing recommendations are a positive outcome of increasing knowledge. 

“Evidence is growing and guidance is evolving on antibiotic use, which is a normal process and a good sign that we are working to improve how we provide care,” he says. “Our knowledge about how best to use antibiotics has changed, but it has changed because we’re learning more, and it’s important that we make sure we are communicating this well to the public.”

Source: University of Utah Health

Strep A Immunity Could Be Acquired via Asymptomatic Infection

This illustration depicts a 3D computer-generated image of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Credit: CDC on Unsplash

Exposure to a mild or symptom-free strain of Streptococcus pyogenes (Strep A) can trigger the body’s immune response and naturally build protection, potentially solving a nearly 100-year-old mystery of immunity.

New Griffith University research, with the help of clinical scientists from the Murdoch Children’s Research Institute (MCRI), investigated how immunity developed over time as infection rates declined with age, suggesting progressive immune protection.

Strep A is a common bug which can cause painful tonsillitis and school sores in young children and teenagers.

If untreated, it can lead to rheumatic fever, rheumatic heart disease and kidney disease, conditions for which First Nations peoples in Australia suffer some of the highest reported rates in the world.

It is estimated 10-20% of children across Australia develop Strep A tonsillitis each year, with some getting the disease multiple times and requiring surgical removal of the tonsils.

By adulthood, most people have developed immunity to Strep A even though most will have only had a few bouts of tonsillitis in their life.

Senior author Associate Professor Manisha Pandey from Griffith’s Institute for Biomedicine and Glycomics said: “How this might happen has never been adequately explained as there are more than 250 distinct strains of Strep A, and immunity to one strain does not provide protection against the others.”

“To address this question, the team investigated the development of immunity using samples collected through a controlled human infection study conducted by MCRI researchers who administered a dose of Strep A which was high enough to cause tonsillitis in most, but not all.

“All participants were treated with antibiotics, regardless.

“Surprisingly, antibodies from the asymptomatic participants not only bound strongly to the exposed strain of bacteria but were able to kill the Strep A germ in a murine model of tonsillitis.”

The findings demonstrated both symptomatic and asymptomatic participants developed robust immune responses to the Strep A strain they were exposed to.

Dr Ailin Lepletier, said it had been known for many years that multiple strains of Strep A were circulating in the community and up to 30% of people had Strep A in their throats without getting sick.

“But we didn’t know this may be providing immunity to these strains, causing silent infections so that by adulthood, we have accumulated antibodies to fight most strains,” she said.

“While a person may not feel sick, their body can still learn how to fight the bacteria and remember it from childhood into adulthood.”

Professor Michael Good AO, said this mechanism of natural immunity may also apply to other common infections.

“While highly intriguing for Strep A, it is unlikely to provide a strategy for a vaccine as it would be necessary to vaccinate against each of the 250 strains,” he said.

Dr Anna Calkin, National Manager of Research at the Heart Foundation, said the findings came from research made possible through approximately $2.79 million in Heart Foundation funding.

“The findings highlight the importance of investing in research that addresses conditions disproportionately affecting First Nations peoples,” Dr Calkin said.

“By improving our understanding of how natural immunity to Strep A develops, this work may contribute to future efforts to prevent rheumatic heart disease and close longstanding health gaps.”

The research team included Griffith University Professor Daniel Kolarich, plus MCRI researchers Associate Professor Joshua Osowicki and Professor Andrew Streer.

The paper ‘Subclinical exposure to Streptococcus pyogenes drives the development of long-lived homologous immunity’ has been published in Nature Communications.

Source: Griffith University

Omega-3 and Low-dose Aspirin Similar to Antibiotics’ Effect Against Severe Periodontitis

Study shows that combining the two compounds with conventional treatment may be a promising alternative, reducing the need for antibiotics.

Photo by Caroline Lm on Unsplash

By Fernanda Bassette  |  Agência FAPESP – A combination of omega-3 and low-dose acetylsalicylic acid (ASA) produced results comparable to antibiotics in treating severe periodontitis. This conclusion is based on a study conducted by researchers affiliated with Albert Einstein Israelite Hospital, Guarulhos University (UNG), the University of Taubaté (UNITAU), and the Ribeirão Preto School of Dentistry at USP (FORP-USP) in Brazil, as well as Harvard University in the United States. The findings were published in May in the Journal of Periodontology and suggest a promising therapeutic alternative for some patients by reducing the need for antibiotics. These findings are particularly relevant in the context of growing global concern about bacterial resistance.

Supported by FAPESP (projects 20/05874-2 and 20/05875-9), the study followed 109 patients with advanced periodontitis over the course of one year. Advanced periodontitis is a chronic inflammatory disease caused by the accumulation of bacteria beneath the gums, affecting the tissues that support the teeth. If left untreated, it can lead to tooth mobility, bone loss, and even tooth loss. 

“Patients with severe disease have very deep pockets, which act as reservoirs for bacteria associated with the disease. It’s a very challenging condition to treat,” says dental surgeon Nídia Cristina Castro dos Santos, the first author of the study and a professor and researcher at Einstein. 

For the study, participants were randomly assigned to one of four groups. All underwent subgingival instrumentation – popularly known as scaling – which is considered the standard treatment for periodontitis. However, they received different complementary therapies.

The control group received placebos of the antibiotics, omega-3, and ASA in capsules identical to those used for the active treatments. A second group received a combination of the antibiotics metronidazole and amoxicillin, considered the therapy with the strongest scientific evidence for severe cases of the disease, administered three times a day for 14 days. The third group took three grams per day of omega-3, in addition to a daily dose of aspirin for six months. The fourth group received a combination of the two strategies simultaneously: antibiotics for two weeks and the omega-3 and ASA protocol for six months. Participants were reevaluated after three, six, and twelve months.

By the end of the follow-up period, about 58% of patients who were treated with antibiotics had met the researchers’ established clinical goal of having no more than four remaining deep periodontal pockets. Among those who received omega-3 and ASA, the percentage was virtually the same: 57.7%. In contrast, in the group that received only scaling and a placebo, the rate was 23.1%. Combining the two strategies, antibiotics and supplementation, didn’t provide any additional benefits.

“The use of antibiotics isn’t considered the gold standard of treatment. Although metronidazole and amoxicillin yield good results in the most severe cases, their use should be evaluated on a case-by-case basis due to risks related to bacterial resistance and possible adverse effects,” says Castro dos Santos. 

These results reinforce a line of research that has been underway for some time. In a previous study also supported by FAPESP and published in the journal Scientific Reports, the researchers observed that omega-3 supplementation reduced inflammation and bone loss caused by periodontal disease in rats, especially when combined with physical exercise. Although the study was conducted in an animal model, it already indicated the nutrient’s potential in inflammatory processes related to oral health (read more at agencia.fapesp.br/54990). 

According to Castro, omega-3 differs from traditional anti-inflammatory drugs in that it contributes to the production of molecules involved in the natural resolution of inflammation and tissue repair, rather than blocking certain inflammatory pathways. Low-dose ASA, on the other hand, was used because it enhances the formation of these mediators. The researchers hypothesised that this strategy would help the body better control the chronic inflammatory process characteristic of periodontitis.

“We imagined that the combination of antibiotics and omega-3 would be most effective in controlling periodontitis in these patients. We also believed that the results for the group that used omega-3 with ASA would be slightly lower than those for the antibiotic group. The result was surprising because the two therapies performed very similarly, paving the way for it to become a treatment option for these patients,” says Castro.

Another finding that caught the researchers’ attention was the persistence of the observed benefits. Even six months after supplementation ended, patients continued to show results similar to those recorded at the end of treatment. According to Castro, this suggests that modulating the inflammatory response may produce lasting effects, although the mechanisms involved are still being investigated.

For dental surgeon Magda Feres, the lead author of the study and a full professor at the Harvard School of Dental Medicine and the Graduate Program in Dentistry at UNG, the results suggest that modulating the inflammatory response may represent a viable alternative for selected patients. “The combination of omega-3 and low-dose aspirin achieved clinical benefits comparable to those of the metronidazole and amoxicillin protocol, opening up a real alternative for those who can’t take antibiotics, especially patients with allergies or intolerance to these medications,” she says.

The researcher adds that the results are especially significant in light of growing concerns about antibiotic resistance, which is considered one of the main threats to global public health. “Demonstrating that it’s possible to treat severe periodontitis by modulating the body’s own response is new and relevant information that helps preserve antibiotics for when they are truly indispensable,” says Feres.

However, the authors emphasise that the results do not imply an immediate change in clinical practice. The study was conducted on patients without significant systemic or oral diseases. Further research is needed to confirm the findings in different populations and to identify which groups can truly benefit from each approach.

According to Feres, some of the answers may come from microbiological analyses currently underway. These analyses are investigating how these therapies influence the composition of bacteria in periodontal pockets. Preliminary data suggest a reduction in disease-associated species and an increase in microorganisms related to gum health. “It’s an important step forward, but not the end of the story. Therefore, the message is one of cautious optimism: we have a promising, scientifically plausible alternative to antibiotics in select cases. Routine replacement will require more evidence,” she concludes.

The article “Immunomodulators, associated or not with systemic antibiotics, to treat periodontitis: A 1-year multicenter, placebo-controlled, double-blind, randomized clinical trial” can be read at aap.onlinelibrary.wiley.com/doi/10.1002/jper.70081.

Source: FAPESP

Lower Dementia Risk Seen with Oestrogen-only Hormone Therapy

Photo by Ravi Patel on Unsplash

Use of hormone therapy later in life was associated with a lower risk of developing dementia, according to a study published August 12, 2026, in Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that hormone therapy prevents dementia; it only shows an association.

“While these findings help us better understand the relationship between hormone therapy use and various markers of dementia, more research needs to be done before we can make recommendations to women about their use of these therapies in relation to their brain health,” said study author Jennifer Bruno, PhD, of Stanford Medicine in Stanford, California. “This study looked back at women who were using hormone therapy decades ago with the timing and type of use differing from what is current practice for most women today, so the results are informative, but they may not apply to today’s standards.”  

For the study, researchers examined medical records from two large data sets. In total, the study reports data from 21 462 female participants from both groups who had clinical tests taken while they were living. A total of 728 participants from one data set completed brain scans or biomarker tests while they were living and 2959 participants from the other data set had autopsies after death, at an average age of 82, to look for signs of Alzheimer’s disease. Across both data sets, participants were followed for approximately three to five years, starting at an average age 71. 

Of the total participants, 1953 participants took hormone therapy and 19 509 participants did not take hormone therapy. Those who used hormone therapy started using it when they were over age 70, on average. The researchers looked only at participants who took oestrogen-only therapy, since previous studies had indicated that oestrogen plus progestin combination therapy may increase the risk of dementia. In current standard practice, oestrogen-only therapy is prescribed only for those who have undergone a hysterectomy due to the risk of endometrial cancer.

Among the group with autopsy information available, participants who had taken hormone therapy were less likely to have signs of Alzheimer’s disease in their brains than those who had not taken hormone therapy. The autopsy assessment used a composite score that measures three hallmarks of Alzheimer’s disease: amyloid-beta plaques, tau tangles and neuritic plaques, which are amyloid plaques surrounded by damaged nerve cells.

Of those who had taken hormone therapy, 18% had no signs of Alzheimer’s disease in their brains at autopsy, compared to 10% of those who had not taken the therapy, and 40% of hormone therapy users had all three signs of Alzheimer’s disease, compared to 51% of those who had not taken the therapy. After adjusting for age, education, genetics, race and hypertension, researchers found that participants who took hormone therapy had 35% lower odds of signs of Alzheimer’s disease at autopsy when compared to those who did not take hormone therapy.  

In a separate analysis using biomarker tests performed when women were living, those who used hormone therapy had levels of amyloid biomarkers in their blood and spinal fluid that indicated less amyloid buildup in the brain compared to women who did not take hormone therapy. Specifically, higher levels of amyloid-beta protein in blood and spinal fluid suggest that less of this protein was being deposited as plaques in the brain.

Finally, use of hormone therapy was also associated with 39% lower odds of receiving a clinical diagnosis of dementia and less risk of showing symptoms of memory problems or decline in functional abilities.

Bruno noted that the study participants who used hormone therapy had an average age of 70, which differs from current standard practice of starting hormone therapy usually in the late 40s to early 50s and stopping it before age 60.

“Despite these limitations, our findings provide evidence of an association between use of oestrogen-only hormone therapy during later life and better outcomes on dementia and brain health,” Bruno said.

Source: American Academy of Neurology

One Month of Eating Vegan Shifts Epigenetics Tied to Aging and Inflammation

A vegan diet reshaped DNA methylation linked to immune cell composition and health-related measures of biological aging

Photo by Pixabay

Researchers from University of California San Diego and University of Freiburg in Germany have found that switching to a vegan diet for just one month can alter the body’s epigenetic landscape in ways associated with reduced inflammation and biological aging. In a randomised clinical trial, participants assigned to a vegan diet vs a meat-rich diet showed changes in DNA methylation – a biological process that regulates whether genes are more or less active – that were linked to immune function, metabolism and cancer-related pathways. The findings, published in the journal MedComm, suggest that dietary choices can rapidly influence molecular processes associated with long-term health.

“Our genes are not our destiny,” said Jerome Mertens, PhD, associate professor of neurosciences at UC San Diego School of Medicine and co-senior author of the study. “The remarkable finding isn’t simply that one diet outperformed another. It’s that the epigenome responded measurably in just four weeks, showing that our biology is far more dynamic – and responsive to everyday choices – than we often assume.”

Diet has long been linked to the risk of chronic diseases such as cardiovascular disease, diabetes and certain cancers. Yet scientists have only begun to understand how food influences the epigenome – the layer of chemical modifications that helps determine which genes are turned on or off without changing the underlying DNA sequence.

To explore these effects, researchers analysed genome-wide DNA methylation patterns in blood samples from 48 healthy adults who participated in a randomized dietary intervention. After following the same standardized diet for one week, participants were randomly assigned to either a vegan diet or a meat-rich diet for one month. Both diets were designed to provide similar calorie intake, allowing researchers to isolate the effects of diet composition rather than weight loss.

The team examined more than 800 000 methylation sites across the genome before and after the intervention. Rather than looking for changes in individual genes alone, the researchers focused on broader biological patterns that changed in response to diet.

The researchers also found evidence that the vegan diet shifted the immune system toward a less inflammatory state. DNA methylation analyses predicted lower proportions of neutrophils – immune cells that drive inflammation – and higher proportions of CD4 T cells, which help regulate immune responses. Those predictions closely matched blood cell measurements collected during the original clinical trial.

“Our genes are not our destiny. The remarkable finding isn’t simply that one diet outperformed another. It’s that the epigenome responded measurably in just four weeks, showing that our biology is far more dynamic – and responsive to everyday choices – than we often assume.”

Jerome Mertens, PhD, associate professor of neurosciences at UC San Diego School of Medicine and co-senior author of the study

“That agreement told us we weren’t just seeing changes on a computer screen — we were detecting real and meaningful biological changes,” said Lukas Karbacher, UC San Diego School of Medicine neuroscience graduate student and first author of the study.

The findings build on earlier evidence that plant-based diets can influence immune function while providing additional insight into the molecular changes that accompany those effects.

In addition to immune signals, the researchers found that the vegan diet was associated with increased promoter methylation in genes involved in several cancer-related and cell growth pathways. Increased promoter methylation can reduce the activity of genes within these pathways, suggesting the diet may influence cellular processes involved in growth and proliferation. The researchers also observed changes consistent with reduced activity in lipid metabolism pathways and increased activity in pathways related to insulin signaling, DNA repair and cellular stress responses.

Perhaps the most striking finding concerned biological aging itself. For this, the researchers examined biological age using epigenetic clocks – a mathematical biomarker that estimates a person’s biological age based on DNA methylation patterns rather than years lived. Two clocks designed to predict health outcomes suggested participants following the vegan diet experienced a deceleration in biological aging over the one-month study period. A third clock, optimised to predict chronological age rather than health outcomes, showed a different pattern, highlighting that epigenetic clocks measure different aspects of aging.

“These findings reinforce the idea that not all measures of biological aging capture the same biology,” said Mertens. “The clocks associated with disease risk and overall health consistently pointed in the same direction, suggesting the dietary changes were influencing pathways tied to health rather than simply the passage of time.”

The researchers caution that the study was relatively small, involving 48 healthy adults, and lasted only one month. Because the observed DNA methylation changes were modest and spread across hundreds of thousands of sites in the genome, larger and longer studies will be needed to confirm the findings and determine whether the molecular changes translate into measurable reductions in disease risk.

While the findings do not demonstrate that a vegan diet prevents cancer or reverses aging, they provide new insight into how dietary choices may rapidly influence the biological processes that underlie inflammation and age-related disease.

“Our study adds to growing evidence that nutrition can shape biology at the molecular level,” said Max Storz, MD, from University of Freiburg Medical Center and co-senior author of the study. “The next step is to understand whether these epigenetic changes persist over time and whether they translate into meaningful improvements in long-term health. That will require larger clinical studies, but these findings provide an important foundation.” Storz also stressed that the findings are not the result of reduced calories, but rather a matter of diet composition.

Read the full study: [A vegan diet epigenetically modulates inflammatory pathways and biological aging: Genome-wide DNA methylation analysis of a one-month isocaloric vegan versus meat-rich dietary intervention]

By Lizelda Lopez

Source: University of California San Francisco

Triple-dose Regimen May Permanently Clear HIV in Infected Newborns

OHSU-led discovery in animal model could advance quickly to clinical trials in people

Research from the lab of Jonah Sacha, PhD, at OHSU, has identified a one-time regimen of therapies for newborns with HIV that, if given within three days of birth, could permanently clear the virus. The research team hopes to use the animal model results to move into a human clinical trials. (OHSU/Christine Torres Hicks)

Every year, more than 120 000 newborns worldwide contract HIV, a global health burden that requires lifelong treatment for millions of people – assuming they have access and can afford it. New research led by Oregon Health & Science University suggests another possibility: a one-time regimen of therapies given to newborns within three days of birth to permanently clear the virus. The research was published in the journal Nature Microbiology.

“The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and chief of pathobiology and immunology at OHSU’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute. “The next step after that is to test if this can work in newly exposed adults.”

The research involved many collaborators and nonhuman primates at both the Oregon and California national primate research centres.

Researchers tested three distinct treatments that were delivered for a few weeks: neutralising antibodies, standard antiretroviral therapy, and an experimental monoclonal antibody known as leronlimab.

Each of the individual treatments has been tried previously and failed to permanently clear the virus – and Sacha wasn’t convinced combining them would work any better. Sacha has worked for years to develop leronlimab, which is designed to block HIV from entering immune cells through a surface protein called CCR5. His longtime OHSU colleague and coauthor Nancy Haigwood, PhD, thought combining existing therapies with leronlimab might be effective.

The study that published today shows she was correct.

Haigwood, a former professor and ONPRC director, is a virologist and immunologist who has specialised in HIV antibody research for decades. “We were astounded and overjoyed, actually,” Haigwood said. “It’s a remarkable result.”

Antiretroviral therapy has already been approved in people, whereas broadly neutralising antibodies and leronlimab are both being tested separately in clinical trials. This new discovery of a one-time, three-part regimen to clear the virus in newborn babies would first need to be tested in clinical trials in people – most likely in newly exposed adults initially – before it would be widely available to constrain an HIV epidemic that continues to kill 600 000 people worldwide each year.

Researchers say they are optimistic, given the anatomical similarity between nonhuman primates and people.

“There was no reason to think this would completely clear the virus,” Sacha said. “It’s one of those things where you test it and, holy cow, it works and you’ve discovered something new.”

Exactly how this approach worked remains unclear, but Sacha and Haigwood said it appears that the combination of therapies is far more potent and effective than each therapy alone. The key appears to be leronlimab’s ability to block HIV from entering immune cells through the surface protein CCR5.

“For reasons we don’t understand, HIV really wants to use CCR5 receptors to infect cells,” Sacha said. “By blocking access, it’s like you’ve kept fuel away from the fire.”

Haigwood uses a slightly different analogy:

  • Turning off the faucet: Antiretroviral therapy doesn’t eliminate HIV altogether, but it minimises its ability to replicate.
  • Mopping up: Neutralising antibodies effectively corral HIV so there is less virus circulating in the body’s blood supply.
  • Sealing off: Leronlimab blocks what’s left of the virus from infecting immune cells – the equivalent of sealing off the room with a water-tight valve.

Haigwood believes the combination appears to be especially potent early in the infection.

“There’s a lot more going on during the first week of infection than we previously thought,” she said. “From this experiment, it looks like there’s a dynamic interaction between the virus and antibodies that takes place as the virus begins to spread.”

Researchers are eager to see whether the combined regimen can be effective beyond 72 hours of the initial infection.

“We only tested out to three days,” Sacha said. “Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?”

By Erik Robinson

Source: Oregon Health & Science University

More Screen Time Since Childhood Linked to Better Cognitive Processing in Adolescence

Photo by Steinar Engeland on Unsplash

A study conducted at the Universities of Jyväskylä and Eastern Finland, found the surprising result that more screen time since childhood was associated with better cognitive processing in adolescence. According to one of the researchers, we should not regard screen time solely as harmful. The most important thing is to find a balance between physical activity and screen time that promotes active thinking.

Adolescents’ scarce physical activity is a major challenge in terms of public health. Sedentary lifestyle has been shown to decrease school achievement, while physical activity is known to promote brain functions especially for adults. However, there is little research evidence about the connections of physical activity and sedentary time in childhood and adolescence with regard to cognitive processing in adolescence, although these life stages are pivotal for brain development. Various factors that influence cognitive processing in childhood and adolescence can be reflected far into adulthood also in terms of educational choices and working life. 

The study investigated how physical activity, sedentary behaviour and screen time from childhood to adolescence are associated with cognitive processing in adolescence and whether there are any sex differences in these connections. In addition, the researchers also examined the role of the intensity of physical activity in this respect. 

Screen time can support thinking and learning 

According to the findings, higher amount of screen time since childhood were connected to better cognitive processing in adolescence.  

“The findings suggest that screen time can support children’s and adolescents’ cognitive processing. Presumably, the essential point here is what kind of things they do in their screen time. Teachers and parents should encourage children to use devices and screens in such ways that promote active thinking, problem-solving, creativity and learning,” states Doctoral Researcher Petri Jalanko from the University of Jyväskylä. 

“We should not regard screen time solely as harmful but seek balance between physical activity and screen time that promotes active thinking,” Jalanko summarises. 

Physical activity and sedentary time associated in complex ways with cognitive processing 

In girls, the higher amount of light-intensity physical activity since childhood was associated with better working memory in adolescence. In boys, then again, higher amount of guided physical activity from childhood to adolescence was associated with better working memory in adolescence. 

Surprisingly, lesser self-reported unsupervised physical activity was connected to better cognitive processing in adolescence. Instead, physical activity or sedentary time as measured by a heart rate and movement sensor were not associated with cognitive processing. The differences may be explained by the fact that the heart rate and movement sensors cannot tell what a person is actually doing during the physical activity and sedentary periods. 

“Our study indicates that the connections of physical activity and sedentary behaviour to cognitive processing are complex and depend on the sex, the type and assessment method of physical activity and sedentary time. Moreover, boys and girls may benefit from different types of physical activity in view of brain health, Jalanko adds. 

“However, we need more intervention studies to find out causal relations and sex differences in this respect. Moreover, it is important to examine more specifically the effects of the intensity of physical activity on changes taking place in cognitive processing.”

The findings are based on an eight-year follow-up of the PANIC study on children’s physical activity and nutrition. The current study involved 124 girls and 136 boys, whose average age was 15.8 years. Physical activity and sedentary behaviour were measured by a device that combined heart rate and movement measurements and also by a survey questionnaire. Learning, attention and working memory were assessed by means of the CogState test battery. The research article is published in the Pediatric Exercise Science journal. 

Source: University of Finland