Daily Archives: June 9, 2022

Diabetic neuropathy, also referred to as peripheral neuropathy, is a condition that encompasses a wide range of clinical pathologies stemming from peripheral nervous system dysfunction in diabetic patients [1]. The most prevalent presenting symptoms include numbness, tingling, and burning in the extremities, with estimates suggesting a prevalence ranging between 6% and 51% among adult patients with diabetes [2]. Although the exact cause of diabetic peripheral neuropathy is not known, several studies have proposed underlying pathophysiologies, including metabolic, neurovascular, and autoimmune mechanisms. The most widely accepted theory is the induction of oxidative stress in the mitochondria caused by hyperglycemia, which results in hyperglycemic damage. This, in turn, causes damage to the endothelial and neuronal cells, compromising oxygen and nutrient supply to the nerves [3].

Neuropathic pain is a challenge to treat, with most standard analgesics not providing sufficient pain alleviation. The management of diabetic neuropathy, therefore, is divided into four pillars and primarily focuses on addressing underlying risk factors for diabetic neuropathy: (a) pathogenetically orientated therapy, (b) symptomatic therapy, (c) near-normoglycemia, and (d) avoidance of risk factors [4], with near-normoglycemia being the primary aim of treatment. The medication route of treatment mainly incorporates antidepressants, antiepileptics, and opioids, with the first-line therapies being tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and anticonvulsants that target calcium channels. Topical agents, including capsaicin and lidocaine, may also be considered [5]. More recently, antioxidants, including flavonoids and alpha-lipoic acid (-lipoic acid) have been proposed as effective interventions in treating diabetic neuropathy [6].

Given the growing body of evidence concerning the role of -lipoic acid in the treatment of diabetic neuropathy, this systematic review aims to evaluate the current literature and make recommendations for further research. The focus is on symptom reduction and the incidence of adverse events following administration of -lipoic acid in this population.

Study Design

The primary objective of this systematic review is to assess the effect of -lipoic acid in the treatment of diabetic neuropathy. Several secondary objectives are also evaluated, including the incidence of adverse effects following -lipoic acid administration.

Search Strategy

This systematic review was carried out in line with the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [7], adhering to the 27-point framework of recommended steps [8]. The literature databases PubMed, Scopus, and Web of Science were searched on March 3, 2022, to extract a list of relevant literature for this review. The search terms (alpha-lipoic acid) AND (diabetic neuropathy) AND (treatment) were used, alongside their relevant synonyms. Table 1 presents the search terms used in the search strategy, as identified by the Population, Intervention, Comparison, and Outcome (PICO) framework (Table 1).

For study selection, the following inclusion criteria set the parameters for eligibility: (1) a study population composed of diabetes mellitus patients with neuropathic pain, (2) randomized controlled trials (RCTs) investigating -lipoic acid, (3) and an appropriate comparison was made in the study. Studies were excluded if they were published in a non-English language. Studies were independently identified to be included in the review by a thorough evaluation of the titles and abstracts of the results from the database searches. The final decision to include a study, however, was based on an assessment of the articles full text. The reference list of the included literature was also reviewed to discover any additional eligible trials for review. Unpublished studies, gray literature, and conference proceedings were excluded (Table 2).

Data Extraction

A data extraction form was formulated in line with the PRISMA recommendations [7]. This permitted the extraction of all relevant data from the literature included in this review. This included author(s), year of publication, patient population, intervention, comparison, study period, outcome measures, results, and any conclusions deduced based on the evidence provided regarding the administration of -lipoic acid among diabetic patients with symptoms of peripheral neuropathy.

Quality Assessment

The authors independently evaluated the quality of each trial using the evaluation form for RCTs developed by the Critical Appraisal Skills Programme (CASP) (http://casp-uk.net). The level of evidence and recommendation for use grades were deduced in line with the Oxford Centre of Evidence-Based Medicine version 2009 (http://cebm.net). The quality of evidence was downgraded if there was a strong risk of bias, imprecision in data collection methods, inconsistency in the findings, indirectness, or publication bias [9].

Identification of the Literature

Incorporation of the search strategy resulted in 759 studies deemed relevant to the objectives of this systematic review, of which eight articles met the inclusion criteria for eligibility. Figure 1 summarizes the flow of literature at each stage of the screening process, with a total of 68 full-text articles being assessed for eligibility once duplicate studies were removed and the citations were screened against the inclusion and exclusion criteria.

Data Extraction

Eight studies comprising 1,500 diabetic patients were evaluated in this systematic review. All studies followed an RCT design. An overview of the data extraction process is presented in the Appendices.

Population

The populations included in the RCTs had diabetes mellitus. Four studies (50%) exclusively investigated the implications of -lipoic acid on type 2 diabetic patients with neuropathic pain, one trial (12.5%) solely included type 1 diabetic patients, and three trials (37.5%) included both type 1 and 2 diabetic patients.

Intervention and Comparison

All trials investigated symptom reduction in diabetic patients with neuropathic pain following the prescription of -lipoic acid; however, the dosage and method of administration varied between studies. Four trials (50%) administered the intervention intravenously (IV), three trials (37.5%) administered the intervention orally, and one trial (12.5%) adopted a combination of both administration methods. The dosages of -lipoic acid administered ranged from 600 to 1,800 mg/day. The most prevalent dosage administered was 600 mg/day, with this approach being adopted in five trials (62.5%). Two trials (25%) had more than one intervention group, with each division receiving a different dose of -lipoic acid, varying from 100 to 1,200 mg/day. All trials used an inert placebo as the comparison.

Outcome

The findings observed were inconsistent with each other concerning the effectiveness of -lipoic acid in the treatment of diabetic neuropathy. Three trials (37.5%) observed a significant improvement in symptoms, including a reduction in the total symptom score (TSS), a reduction in the symptoms of autonomic neuropathy, and improvements in measures of nerve conduction. The remaining five trials (62.5%), in contrast, did not observe any notable results when compared to the baseline or the control group. Moreover, the lack of consistent data collection methods prevented a thorough comparison of the reported outcomes. All studies found -lipoic acid to be a safe and tolerable intervention, with no reported adverse effects.

Risk of Bias

The Oxford Centre of Evidence-Based Medicine risk of bias assessment is presented in Table 3, with all trials presenting high-quality evidence and moderate recommendations for use given the nature of their design. The CASP tool did not identify any areas for concern, with a low risk of bias being observed across all included studies. This represents the overall strength of this systematic review and its findings.

This systematic review aimed to evaluate the effectiveness and safety of -lipoic acid in the treatment of neuropathic pain in diabetic patients. We observed that the administration of -lipoic acid offers an alternative intervention for the treatment of diabetic neuropathy and is a safe and tolerable approach. However, significant findings were only observed in three trials included in this review, with the remaining literature failing to present any notable evidence. Hence, further trials are warranted to corroborate or contradict the hypothesis that -lipoic acid is an effective intervention for the treatment of diabetic neuropathy.

A review by Vallianou et al. proposed that -lipoic acid achieves its symptom alleviation by delaying or reversing peripheral diabetic neuropathy using its antioxidant properties. In particular, -lipoic acid increases glutathione, an endogenous antioxidant involved in antioxidant defense, nutrient metabolism, and the regulation of cellular events [18,19]. Moreover, the literature highlights that glutathione deficiency contributes to oxidative stress, which plays a crucial role in the pathogenesis of diabetic neuropathy [20]. However, the literature does suggest that the effect of -lipoic acid is greater when used with conventional treatment. A trial by Karalis et al. investigating the effect of -lipoic acid as a combination treatment on diabetic peripheral neuropathy in 148 type 2 diabetics provided evidence in this respect. The peripheral neuropathy development score significantly decreased among all participants following the administration of a combination of treatments, including -lipoic acid at 600 mg/day, gliclazide, sodium-glucose-linked transporter 2 inhibitors, metformin, and glucagon-like peptide 1 analogs. Treatment was monitored over eight months. Collectively, these findings highlight the beneficial impact of -lipoic acid when used as part of a combination regime in patients with type 2 diabetes experiencing neuropathic pain [21].

Han et al. conducted a systematic review and meta-analysis of RCTs that investigated nerve conduction in diabetic patients with peripheral neuropathy. The findings of this review supported and corroborated the evidence presented in our review, observing significant improvements in only a handful of the included studies. Moreover, this review also reported on the lack of consistent methodologies and poor methodological quality, which resulted in weak evidence being presented [22].

Despite the strengths of this review, such as only including RCTs, there were several limitations that must be considered. First, we exclusively investigated the implications of -lipoic acid as a standalone treatment for diabetic neuropathy, excluding any trial that incorporated this intervention as a combination treatment. This may provide a rationale for the limited evidence observed concerning the sole beneficial effect of -lipoic acid on neuropathic pain. Previous trials, such as that of Wang et al., found significant improvements in diabetic peripheral neuropathy symptoms when -lipoic acid was combined with epalrestat [23]. Future reviews should consider this limitation and compare the patient outcomes of -lipoic acid alone and in combination with current treatments for diabetic neuropathy. Second, the lack of consistent data collection methods across the included trials negated a meta-analysis from being conducted; hence, we were unable to quantitively evaluate the effect of -lipoic acid on the occurrence of diabetic neuropathy.

Based on the majority of evidence from this systematic review, we conclude that the use of-lipoic acid alone provides no significant improvement in the treatment of neuropathic pain among diabetic patients. However, it is considered a safe and tolerable treatment option that may result in some neuropathic symptomatic reduction. Further future trials could incorporate this intervention as a combination with current treatments for diabetic neuropathy considering its notable efficacy and good safety profile.

More:

Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review - Cureus

The largest event in the UK to focus on the benefits of a healthcare system that combines conventional medical treatment with integrative complementary methods attracts world-renowned speakers and doctors, therapists and complementary health practitioners from around the globe.

London is to host the inaugural Integrative and Personalised Medicine (IPM) 2022 congress, the largest event in the UK focusing on the benefits of a patient-centred approach to healthcare that combines conventional treatment with integrative, functional, lifestyle, holistic and complementary methods, resulting in better patient outcomes.

Taking place in-person at the Queen Elizabeth II Centre, London, from 16th to 18th June 2022, the IPM congress features an impressive line-up of speakers including BBC presenter and author, Dr Rangan Chatterjee; scientist and author, Prof Tim Spector; and neurologist Dr David Perlmutter, recognised as one of the USAs most influential physicians.

The three-day event combines a world-class international exhibition and three conferences: the already established College of Medicines Food on Prescription conference, a new Whole-Person Health conference and an Integrative Mental Health conference. It brings together medical and health practitioners from a variety of different fields to encourage the building of a multidisciplinary approach to healthcare where all practitioners involved work together as a team.

IPM 2022 congress Chair and Chair of the College of Medicine, Dr Michael Dixon believes that, post Covid, there is a growing recognition that we need to look at a new way of approaching healthcare. He states:

Medicine, as we know it, is no longer affordable or sustainable, nor is it able to curb the increase in obesity, mental health problems, and most long-term diseases. It is now time for Integrative Care to take centre stage. Combining the best of our current medicine with an approach that enhances our natural abilities to self-heal and stay healthy using lifestyle and a wider range of therapies.

It enables us to reconnect with ourselves, our patients and within our communities, and to recognise the potential of our social and physical environment to heal and enable us to live healthier and happier lives. This conference is a clarion call for Integrative and Personalised Medicine, and marks the dawn of a new era of Post Modern Medicine.

Research evidence into the health benefits of integrating different types of medical, lifestyle, holistic and complementary interventions is growing. In September 2021, the UK Government published a report on the findings of Former Chief Pharmaceutical Officer for England, Dr Keith Ridge, on over-prescribing in England. The report found that 10 percent of prescription items dispensed through primary care are either inappropriate for patients needs or that they could be better served with alternative treatments. As a consequence the College of Medicine launched its Beyond Pills initiative to reduce unnecessary drug prescribing, expand social prescribing, benefit patients' health, support patient empowerment and save money. It also benefits medical professionals, many of whom may have entered medicine to help patients recover but often find themselves in a position of symptom management that is dependent upon the culture of pills. An integrative and personalised approach to medicine provides them with additional treatment options to help their patients. The campaign will be explored in more detail during a panel discussion on day one of the conference.

Another key session of the IPMs Whole-Person Health Conference on day one, focuses on ways to enable our doctors and nurses to flourish. The Whole-Person Health Conference will be chaired by Dr Elizabeth Thomson, CEO of the National Centre for Integrative Medicine, and this session includes some of the leading names in integrative, personalised, functional and holistic medicine, such as Prof Dame Clare Gerada, President of the Royal College of General Practitioners, Dame Donna Kinnair, previous Director General of the Royal College of Nursing and Vice Chair of the College of Medicine, Dr Susanna Petche, Functional Medicine Doctor and GP, and Dr Ally Jaffee, NHS Junior Dr, Co-founder Nutritank, NHS Clinical Entrepreneur & 2021 Diana Award recipient. Together they will leave Prof Dame Gerada and Dame Kinnair will lead a discussion on keeping medical professionals themselves healthy to enable them to provide quality healthcare to others. Traditionally, the medical field has faced a culture where sacrifice is prioritised over self-care, leading to severe risk of burnout, but an integrative and personalised approach to medicine, with an emphasis on self-care and wellbeing, can also support the practitioners themselves.

During the Integrative Mental Health Conference on day two, the evidence and impact of integrative medicine on mental health is explored. The event will highlight the benefits of this growing approach to mental illness management that combines nutrition, social prescribing, psychotherapy, cannabinoids, psychedelics and a range of evidence-based complementary therapies to help address the worlds growing mental health crisis.

The Food on Prescription Conference takes place on day three of the congress, marking the fourth year for the College of Medicine's annual one-day conference. It is the leading UK event on food, lifestyle and medicine, and is a must attend for all healthcare professionals, who want to know how to create a healthier future for patients and the wider community.

The incredible line-up of speakers over the three days draws on experts from the conventional and integrative fields of healthcare from around the world. In addition to the aforementioned speakers, the event welcomes Dr Dean Ornish, Doctor, Author, Researcher and Advisor and Clinical Professor of Medicine at the University of California, San Francisco; Prof Robert Thomas, consultant Oncologist at Addenbrookes and Bedford Hospital; Dr William Li, world-renowned physician, scientist and author of EAT TO BEAT DISEASE The New Science of How Your Body Can Heal Itself and Dr Aseem Malhotra, Consultant Cardiologist, best-selling author & Chair, Public Health Collaboration. The event also includes free exhibitions and workshops.

The tide change towards a more holistic approach to restoring and maintaining health is growing, particularly among younger doctors and newly trained GPs, according to Dr Dixon:

"They have a new attitude towards healthcare. They are not interested in whether something is viewed as conventional, complementary, functional or lifestyle, they are just looking at what works for their patients. Through this conference, we aim to capture that sense of hope, open-mindedness, and patient-centred care. By sharing clinical experience, knowledge and ideas, we will see the start of a new revolution that strips away the labels and focuses on whole-person, patient centred care. This congress will bring together some of the best talents, so we can pool our knowledge and resources and leave re-invigorated and inspired.

For further information and to register, visit: http://www.ipmcongress.com

The full line up of speakers can be found at http://www.ipmcongress.com/conference/speakers

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World-renowned Health Experts to gather in London at Integrative and Personalised Medicine 2022 Congress - Pressat