Summary
Highlights
Dr. Joel Brind challenges the common understanding that inflammation is the immune system's first response to both infection and injury. He asserts that inflammation is beneficial only in the case of infection, doing no good for injuries. He attributes excessive inflammation from injury to a modern diet low in glycine, an amino acid crucial for moderating immune responses. Glycine helps keep M2 macrophages (quiescent, cleanup cells) from transforming into M1 macrophages (which release toxins in response to infection), unless an actual infection is present.
Dr. Brind began experimenting with 10 grams of glycine daily in 2008 following research into methionine restriction at the Orentreich Foundation. Studies found that rats on a methionine-deficient diet lived 30-40% longer. While methionine restriction is difficult to maintain, glycine was identified as a substrate used to clear excess methionine. The hypothesis was that supplementing with glycine could mimic the life-extending benefits of methionine restriction by facilitating methionine clearance.
Further research by Thurman's group in the 1990s revealed that glycine acts through a classical glycine receptor found in white blood cells (macrophages), platelets, and endothelial cells. This receptor, similar to one in the central nervous system that promotes sleep, helps prevent exaggerated inflammatory responses. Dr. Brind's personal experiences, such as falling on his tailbone and getting a severe sunburn while supplementing with glycine, demonstrated that he experienced healing without the accompanying inflammation, confirming his hypothesis that adequate glycine levels prevent unnecessary inflammation from injury.
Dr. Brind argues that modern diets contribute to a functional glycine deficiency. While glycine is considered 'non-essential' because the body can produce it, he contends the body cannot produce optimal amounts, especially given dietary changes like consuming muscle meat without the glycine-rich bones and connective tissues. This dietary imbalance leads to an excess of methionine (from muscle meat) and a deficit of glycine, exacerbating the need for glycine to clear methionine and stripping the body of glycine needed for other functions, including inflammation control.
Glycine's anti-inflammatory effect is not primarily biochemical but cellular. It binds to glycine-gated chloride channels in cell membranes, allowing negatively charged chloride ions to enter cells. This process hyperpolarizes the cell, preventing depolarization and activation of M1 macrophages, which would otherwise trigger an inflammatory response in the absence of infection. Essentially, glycine acts as a 'hand on the valve,' maintaining cellular stability and preventing inappropriate or excessive inflammation.
Dr. Brind reiterates that while inflammation is a critical response to infection, helping the body fight off pathogens, it is entirely damaging in the case of injury. He explains that inflammatory agents like hydrogen peroxide, released during inflammation, are toxic and hinder healing rather than aiding it. With sufficient glycine, the body can differentiate between actual threats (infections) and injuries, mounting only a necessary, controlled response to infection and allowing injury to heal painlessly without inflammation.
Dr. Brind connects glycine deficiency to COVID-19 comorbidities such as advanced age, obesity, and diabetes. These conditions are associated with lower glycine levels. In individuals with severe glycine deficiency, the body's inflammatory response to infections like COVID-19 can become uncontrolled, leading to a 'cytokine storm' and severe outcomes. He shares anecdotal evidence of glycine supplementation preventing severe respiratory symptoms during COVID-19 infections, suggesting its role in modulating immune overreactions.
Glycine is extremely safe, with studies showing no lasting harm even at very high doses (up to 100 times normal plasma levels) during surgical procedures involving glycine irrigation. While some individuals may experience transient gastrointestinal upset or dizziness, these are rare and mild. Dr. Brind recommends around 10 grams per day for adults, which can be achieved through supplements or glycine-rich foods like gelatin and collagen. For children and pets, dosages can be adjusted proportionally to body weight.
Dr. Brind addresses concerns about glycine's interaction with cancer. Early studies suggested glycine might promote cancer growth in cultured cells, but these findings were later retracted or misinterpreted. He explains that cancer cells, evolving in methionine-rich and glycine-deficient environments (common in modern diets), become efficient at utilizing available glycine. However, it's impossible to lower glycine levels enough to starve cancer cells without harming normal body functions, as glycine is essential for numerous biological processes.
A Cleveland Clinic study in 2015 identified a genetic condition where individuals (specifically women) with a partial deficiency in a glycine-metabolizing enzyme (CPS1) had higher circulating glycine levels and a significantly reduced risk of major adverse cardiac events (heart attacks and strokes). This suggests that higher glycine levels may offer protection against cardiovascular disease, potentially by acting as a natural blood thinner and inhibiting platelet aggregation.
Dr. Brind concludes by emphasizing that glycine, despite being labeled 'non-essential,' is crucial for optimal health, particularly for immune function and inflammation control. He advocates for glycine supplementation due to its scarcity in modern diets which prioritize muscle meat over collagenous tissues. He strongly encourages individuals to try glycine, whether through supplements, gelatin, or collagen peptides, for its potential benefits in reducing unnecessary inflammation and enhancing overall well-being.