Acetyl-l-carnitine & Mental Health 🧠
Depression is estimated to affect a staggering 350 million people around the world, and has been ranked as the second leading cause of global disability.
Unfortunately, depression is both pervasive and very difficult to treat.
A tremendous portion of people battling depression (perhaps close to half) are resistant to available pharmaceutical treatments, which has driven interest in alternative therapy options.
It is thought that one of the core pathophysiological mechanisms that underlies major depressive disorder is impairment of neuroplasticity. In animal models, exposure to intense stress leads to a long-term downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus, triggering a state that mirrors depression in humans.
This is where acetyl-l-carnitine enters the picture. In rodents subjected to social stress, ALC has been shown to prevent stress-induced deterioration of levels of neurotrophic factors.
But does ALC promote resilience similarly in humans? Well, large-scale trials have yet to be performed, but preliminary evidence is promising.
This Week’s Research Highlights
Researchers at Weill Cornell Medicine and the Icahn School of Medicine at Mount Sinai recruited 71 patients with major depressive disorder, as well as 45 age- and sex-matched control participants who did not have depression. All participants underwent clinical and psychiatric assessments, and plasma levels of ALCAR as well as free carnitine were measured. The researchers found that levels of ALCAR — but not free carnitine — were significantly lower in patients with MDD, compared to healthy controls (8.3 μmol/L in controls, vs 6.1 μmol/L in patients with depression). Furthermore, among the patients, the lowest levels were found in those with the most severe depression, earliest age of onset, and in those with a history of childhood trauma.
To determine whether restoration of ALC via supplementation can ameliorate depression in humans, an international team of researchers conducted a systematic review and meta-analysis of 12 randomized controlled trials, with a total of 791 participants. First, they analyzed pooled data from nine RCTs that compared ALC to placebo or no intervention, and found that ALCAR significantly reduced depressive symptoms, but not in younger subjects. Then, they examined the remaining three RCTs, which compared ALC to antidepressants. ALC demonstrated similar effectiveness in reducing depressive symptoms compared to established antidepressants, but with dramatically lower odds of adverse effects. Notably, subgroup analyses revealed that ALC was more beneficial to older adults — a key finding since conventional antidepressant treatment has been linked to more severe negative outcomes in the elderly.
Random Trivia & Weird News
Many modern consumer products that we take for granted today originate from military research. There are few things that drive innovation more effectively than war. DuPont chemist Roy Plunkett stumbled upon polytetrafluoroethylene when he was performing experiments to develop better refrigerators. The new polymer, which was simultaneously very slippery and inert to other chemicals, was first used in the production of nuclear material in the Manhattan Project.
Years later, French engineer Marc Grégoire introduced "Tefal" pans, the first cookware lined in Teflon to prevent sticking.
Podcasts We Loved This Week
- Stephan Guyenet: How to treat obesity — Nutrition, surgery, semaglutide (Wegovy®), and more. Via the Reason & Wellbeing Podcast.
- Orla O'Sullivan: The gut microbiome in health and sport. Via Inside Exercise.
Products We Are Enjoying
There is perhaps no better and more cost-effective supplement than creatine. It is best known for its impressive effects on acute exercise performance, however it may also improve your brainpower, and even help with depression. For some more info on the benefits of this under-appreciated supplement, check out this article.
humanOS Catalog Feature of the Week
“If sleep doesn't serve an absolutely vital function, it is the greatest mistake evolution ever made.” —Allan Rechschaffen.
In this course, we take a look at sleep in the modern world, and the role of technology and lifestyle in contemporary sleep patterns. Particularly, this course zeroes in on how sleep affects facets of mental performance, such as attention, memory, decision-making, and emotion regulation.
For example, past research has shown that lack of sleep makes it harder for entrepreneurs to assess business ideas, and people with insomnia have a harder time focusing and shutting out distractions compared to people who sleep well. Finally, we go into some relatively easy things that you can do to get better sleep — starting tonight.