Chelation therapy in Diabetes

What is Chelation Treatment?

Chelation therapy is defined as using a medicine, either herbal, nutraceutical, or pharmacological, in order to "chelate" or to "claw" a metal ion. When we use specific chelators such as DMSA (dimercaptosuccinic acid) or EDTA (ethylene diamine tetra-acetic acid) we target specifically heavy metal toxins. These heavy metals are preferentially bound to these chelators as they have a higher affinity for the compound. Once bound, the complex is excreted usually into the urine, depending on the agent used.

How does chelation fit into general naturopathic medicine?

Chelation therapy is practiced by many naturopathic doctors, as well as both environmental medicine focused practitioners and functional medicine practitioners. In the case of naturopathic medicine, chelation fits into the realm of a detoxification therapy. While everyone practices naturopathic medicine in a unique way, the original principles of naturopathic medicine seek wellness by putting a focus nutrition and detoxification as the building blocks in which we support the body healing itself. The aim of detoxification is to remove any obstacles that are slowing or preventing the body from healing itself.

Evolution of theories for circulation use

When I first started using chelation therapy many years ago, I had used it mainly in the context of treating circulation. The idea and theories in how it may be beneficial focused on the removal of heavy metals that may be contributing to inflammation and oxidative stress. This oxidative stress likely contributes to the development of plaque in the arteries, as well as contributes to the instability of the plaque which can lead to a clot. There were also older theories about specifically sodium EDTA chelating calcium out of calcified plaque directly, but likely the mechanism is much more complex as free calcium is available in the blood itself to be chelated and would theoretically saturate sodium EDTA. With the results from the large National Institutes of Health study on the "Trial to Assess Chelation Therapy" (TACT trial) showing a positive benefit in chelation, mechanism was not investigated as much but did show that chelation was useful to reduce death and cardiac events (most likely and most useful in diabetics who had already had an ischemic event).

Experience of it in general detoxification in complex illnesses

My practice had evolved over the years where I did not see as many patients with circulatory issues as their primary complaint. Instead, I saw other types of complex patients who largely had unexplained symptoms. We would like into triggers for their symptoms, including stealth or low grade infections, mycotoxins, persisting neurological changes such as central sensitivity, immune imbalances, and occasionally heavy metals. In these patients, while we would sometimes find a mild elevated body burden of heavy metals (often by blood testing), it was less common that this was a main contributing trigger to their illness. Treatment of reducing the metal burden did not make a big difference in their symptoms, at least not as a single therapy and not in a shorter time frame (months). It may have helped to lower their overall body burden of stressors, but as a single therapy it would rarely be enough in this patient population.

General reduction of oxidative stress

Reduction of heavy metals would contribute to a reduction of overall oxidative stress. Oxidative stress is like "rusting" - it contributes to free radicals that if chronic, may be too much for the body to adapt to in a healthy way.

Importance in diabetics for managing oxidative stress

This is where chelation is likely a beneficial add on treatment. Diabetics are prone to increased oxidative stress as well, but most importantly, diabetes creates problems mainly when the elevated sugar levels "stick" to things in the body and vasculature. These are called advanced end glycation products, which contribute to the increased atherosclerosis and build up in diabetics arteries. One of the most broad and general studies looked at population data in 9537 adults in the US and confirmed at the top down level that increased metals were associated with both obesity and diabetes:

Background: Some heavy metals (e.g., arsenic, cadmium, lead, mercury) have been associated with obesity and obesity comorbidities. The analytical approach for those associations has typically focused on individual metals. There is a growing interest in evaluating the health effects of cumulative exposure to metal mixtures. An increase in ERS from 10th percentile to 90th percentile in the overall study population was significantly associated with 4.50 kg/m2 (95% CI: 4.06, 4.94) higher BMI, 4.16 mm (95% CI: 3.56, 4.76) higher skinfold thickness, and 4.11 kg (95% CI: 0.83, 7.40) higher total body fat, independent of age, sex, race/ethnicity, education, smoking status, physical activity and NHANES cycle (Ps < 0.05). Significant associations of ERS with both hypertension and T2DM were also observed (Ps < 0.05). This study looked at blood levels of metals, which has been my preferred way of looking at how likely treatment would help in patients. Another study looked specifically at blood lead levels being associated all-cause mortality, cardiovascular mortality, and ischaemic heart disease: An increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17–1·60), cardiovascular disease mortality (1·70, 1·30–2·22), and ischaemic heart disease mortality (2·08, 1·52–2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9–26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5–39·5) for cardiovascular disease mortality and 37·4% (23·4–48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease. Interpretation: Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure.

While these two population based studies show correlations of metals with diabetes and circulatory problems respectively, and there is good mechanistic data on how metals contribute to these problems, it is different to look at whether the treatment of reducing these metals by chelation improves these outcomes.

Information Specific to Circulation

Unveiling the Role of Metals in Cardiovascular Diseases

In the realm of cardiovascular health, the impact of heavy metals like lead and cadmium has become a subject of growing interest.

1. Metals as Cardiovascular Culprits

Metal displacement of essential minerals appears to be a key player in cardiovascular health. Studies have associated lead with hypertension, stroke, myocardial infarction (MI), and increased mortality. What's more alarming is the long half-life of these metals in the body - up to 30 years for lead and cadmium. These metals tend to accumulate in vital organs such as the kidneys, liver, and especially the bone, potentially contributing to various cardiovascular conditions.

2. Historical Perspectives

As far back as 1886, researchers noted a correlation between arterial thickening and aging in association with lead exposure. In 1956, Clarke et al published a study "Treatment of Angina Pectoris with disodium EDTA". At this time, no statins or aspirin was available, and the main treatment was symptomatic with nitroglycerin. Most patients improved.

3. Population Studies and Meta-Analyses

NHANES population studies uncovered links between cadmium and peripheral artery disease, while a meta-analysis involving 37 studies demonstrated a linear dose-response relationship. Exposure to arsenic, lead, cadmium, and copper was associated with an increased risk of both cardiovascular disease (CVD) and coronary artery disease (CAD).

Heavy Metals may be a modifiable risk factor in cardiovascular disease, especially in diabetics

The Trial to Assess Chelation Therapy (TACT) provided surprising results, challenging initial expectations. Administering chelation therapy to a post-heart attack patient population demonstrated a reduction in cardiovascular events comparable to statin therapy. Interestingly, the benefit of risk reduction continued after chelation was completed (usually a series of 40 infusions) - indicating that there was a "reset" that was occurring. Of note, this is only one risk factor, not a replacement for reduction of other risk factors. For example, the patients (and placebo group) in the trial were treating other risk factors as well, including lowering LDL cholesterol, inhibiting platelets, addressing high blood pressure. There were four arms to the study: chelation and oral vitamins, chelation and oral placebo, placebo chelation and oral vitamins, placebo chelation and placebo vitamins. Importantly, the patient population in this study were:

• age older than 50
• secondary prevention; in this case patients had a previous heart attack that was at least 6 weeks earlier (these were higher risk patients)
• kidney function by creatinine testing was good
• most patients in all groups were on conventional therapy such as statins The results showed a clear benefit for chelation. The researchers were conventional cardiologists and were expecting negative results.

  1. Targeting Diabetes: A Black Swan Event

  One of the main researchers, Dr Lamas, has talked about this as a possible "black swan event". An unexpected revelation emerged when analyzing patients with diabetes. Chelation therapy demonstrated a remarkable 41% relative risk reduction in the primary endpoint, effectively nullifying the added risk associated with diabetes. The reduction in all-cause mortality, myocardial infarction, and revascularization was particularly pronounced in diabetic patients. All cause death was reduced by 43%, heart attack by 50%, and revascularization procedures by 33%. The number needed to treat to prevent 1 event was 6 patients.

  2. Mechanisms and Beyond

  The TACT 2 trial, initiated in 2016, delves deeper into the mechanisms of chelation therapy. The study focuses on post-MI diabetic patients, aiming to uncover the intricate relationships between chelation, metal levels, and cardiovascular outcomes. Early results from TACT 1 and related studies suggest potential benefits in limb ischemia, cognitive function, and in peripheral artery disease. For example, despite the clinically significant reductions in risk of events in the TACT trial (death and cardiovascular events) in diabetics, their sugar levels and medication use were unchanged. Similarly, in peripheral artery disease the improvements were much faster than would be expected if the effect was from controlling sugar levels.

Summary

While detoxification in general is often a component of a naturopathic approach, specifically chelation therapy with EDTA is an option for treating patients with circulatory problems. The best evidence is to prevent a second event in diabetics. These patients, if also on conventional therapy, may experience a roughly 41% reduction in death or significant event. Patients with peripheral artery disease where the smaller blood vessels and microvasculature are affected may improve with chelation as well. If I have a patient who is older than 50, has diabetes, and is interested in preventing a second cardiovascular event, then chelation therapy is likely a good option to discuss. If I have a patient with peripheral artery disease and thus significantly compromised circulation to the extremities, I would likely discuss this as an option for treatment as well. In other patients, running a blood level for heavy metals can help to assess their body burden and whether or not treatment would be likely to help.

For an excellent seminar lecture on chelation therapy by Dr Lamas, one of the main researchers in the TACT and other trials on chelation therapy, see: