In-house Research: The Administration Of Low Dose Naltrexone (LDN) For Those With Multiple Sclerosis (MS)

Single intervention, observational research using GlycanAge testing and an MS Symptom Severity Questionnaire (SSQ), conducted at Harpal Clinic, London, England

Harpal Clinic
Research director: Dr Harpal Bains
Research manager: Victoria Marshall
Medical team: Dr Klaudia Raczko, Dr Nathan Curran, Dr Nikita Grover
Contract manager: Ginny Laramee

Sponsors: GlycanAge, Harpal Clinic, Roseway Labs

Introduction

In January 2023 we excitingly began in-house research looking at the impact that Low Dose Naltrexone (LDN) may have for those with Multiple Sclerosis (MS). Completing research was a first for us, which turned out to be an incredibly interesting and informative endeavour for our team.

What is LDN?

LDN is an off-label treatment that encourages the body to produce its own feel-good transmitters like endorphins through a negative feedback mechanism in the body. These endorphins can help optimise the immune system and modulate it where it is hyperreactive, such as in autoimmune conditions. LDN has been used for a wide range of health concerns in patients with autoimmune diseases, cancers, HIV, MS, Systemic Lupus Erythematosus (SLE), Crohn’s and ulcerative colitis amongst others. Prior to the use of low doses of naltrexone (doses between 0.5-4.5mg), naltrexone was used in much larger doses (50-100mg) to help support people with alcohol dependency. The medical literature surrounding LDN is steadily growing, meaning that its off-label clinical application has widened. Given its extensive previous use at higher doses, you’ll often find LDN described as having a high safety profile in studies.

What is an off-label drug?

According to the National Institute for Health and Care Excellence (NICE): “Medicines can be prescribed if they don’t have a licence (unlicensed) or for ‘off-label’ use. Off-label means that the person prescribing the medicine wants to use it in a different way than that stated in its licence. This could mean using the medicine for a different condition or a different group of patients, or it could mean a change in the dose or that the medicine is taken in a different way.”

Another example of an off label medication people may be familiar with is Semaglutide (Wegovy). Although this medication was initially approved to help manage Type 2 diabetes, it is now being prescribed as an off-label medication to support weight loss.

Research objective

We see many patients looking to use LDN at our clinic, both within functional medicine capacity as well as for longevity-associated and preventative healthcare; meaning that our team is incredibly well versed in supporting patients wishing to use LDN.

The scientific literature looking at LDN and MS is one of the most prominent areas of research for off-label use of LDN. The primary objective of the research was to determine if GlycanAge scores, individual glycans or any GlycanAge traits show any significant changes with LDN administration in a small cohort of patients with MS. Secondary to this, we were also looking to see if there is an association with the aforementioned glycan parameters and MS symptoms in the same group – measured using our carefully curated symptom severity questionnaire (SSQ).

Data collection types

Our data collection included; GlycanAge testing, our SSQ and a personal diary kept by each participant.

GlycanAge Testing

GlycanAge testing has become a prominent health optimisation test in recent years, providing an accurate biological age for individuals. It also provides an expanded report, showing a deeper analysis of a person’s individual glycan activity.

Glycans are complex carbohydrate molecules and are one of four building blocks of life (alongside proteins, lipids and nucleic acids). They are involved in the inflammatory response, including immune cells of innate and adaptive immunity. But glycans do much more than decorate proteins, as they modify the structure and function of proteins – which is why they play such an important role in various biological and physiological processes. Some of the most interesting glycans are the ones that are attached to an IgG (immunoglobulin G). IgG is the most abundant immunoglobulin and functional protein within the adaptive immune system. IgG glycans are closely associated with low-grade inflammation, making them valuable indicators of biological age and healthy ageing – especially if we wish to take a preventative approach to medicine.

Symptom Severity Questionnaire (SSQ)

Our SSQ helped us to initially find patients that met our exclusion and inclusion criteria. The questionnaire was also repeated at each of the three timepoints by each participant. The SSQ included baseline demographics, MS-related questions (e.g., MS subtype and length of disease onset), as well as relevant lifestyle questions.

Personal Diary

Although our SSQ and GlycanAge testing were our primary measurements, we also supplemented this by giving each participant a personal diary to complete each week. It allowed participants to make a note of any changes, and keep a log of their LDN titration.

Conclusion

• Albeit a small cohort, we hope that our initial findings and interest in LDN and GlycanAge testing will be in some way beneficial to future research.
• It can be common for those starting LDN to experience fluctuations in their symptoms as the immune system begins to be influenced by LDN’s mechanism of action in the body. Not all patients experience a level of exacerbation of their symptoms in the early stages and it is not always indicative of how well the medication will work overall. However, it is important for patients to understand this when they begin the process of taking LDN for the first time to reassure them of its normality, and also when we look at the research data we have and the potential impact this may have had.
• Two Glycans (P14, P27) stood out as having changes significant enough at month 9 to warrant further research (Fig.1).

Fig.1 Prominent glycan structures

Fig.2: SSQ analysis

• Physical symptoms warrant further research with better methods of charting symptoms as opposed to patient-reported changes. This is because, whilst overall the symptoms showed improvement, some symptoms (especially muscle stiffness and spasm) worsened. It is hard to tell if the worsening of symptoms is merely a perception issue because other symptoms have improved so much or if there is actual worsening. Overall however, results are very encouraging (Fig.2).
• Mental symptoms demonstrated a significant improvement with most of the improvement taking place later. This demonstrates the need for patience for both the clinician and the patient. We hope that this data will give patients hope that if they persevere, things can improve significantly (Fig.2).
• Initial emotional improvements were considerable and continued to improve for most of the parameters measured. There was regression in some aspects, including depression and anger. Once again, an ability to quantify this better would be of great benefit as it is difficult to differentiate where the regression is real or if it is due to disappointment after an initial period of elation where symptom improvement was so significant. Overall however, the changes are clearly notable (Fig.2).
• Our research demonstrated that LDN improved many aspects of disease progression and symptomology and gave a deeper understanding towards the timescales patients and clinicians can expect for new MS patients starting on this therapy.

We would like to say a special thank you to all of our participants, co-sponsors GlycanAge and Roseway Labs, and the whole team at Harpal Clinic for making this happen.