Anxiety: A Metabolic Disorder?

Much as anxiety commandeers thought processes— jump-starting bouts of worry, demanding hypervigilance, imposing a sense of danger—it is a physiologic state, a response to detection of threat somewhere in the environment, uncomfortable enough to keep people on the knife edge of arousal, prepared for the ancient imperative, fight or flee. Sure, diagnosis as it’s currently constituted relies on symptoms from the neck up, but it is biological processes affecting every cell in the body that drive anxiety disorders, now the most prevalent psychiatric condition in the U.S..

As sensors monitor the internal (a process called interoception) and external environment, the amygdala flags potentially threatening stimuli—the rustle of a snake, a knot in the stomach, the angry demeanor of a stranger—and puts the whole body on alert. It rivets attention to whatever stimulus set it off and activates the body to defend itself.

The amygdala instantaneously signals the hypothalamus, which prompts the adrenal glands to release adrenaline. Breathing quickens and heart rate rises to rush oxygen to muscles so that you can take action as needed.

But adrenaline does much more—it alters body metabolism to underwrite action. It triggers the release of glucose and fats from storage sites in the body. The nutrients pour into the bloodstream, delivering fuel to all the cells in the body. At the same time, the hypothalamus orders the adrenals to release the steroid hormone cortisol, which stimulates fat and carbohydrate metabolism to provide an ongoing source of energy.

Repeated activation of the stress response takes a toll on body and brain. Anxiety is one result, the mind stuck in a state of apprehension as worry caroms through the brain, impairing and even impeding the ability to function.

Contemporary medicine puts the mental symptoms of anxiety in the big tent and deems it a psychiatric disorder, prescribing psychoactive treatments—psychotherapy and neuroactive medications. But there is another view emerging—that anxiety is essentially a physical state and that its roots are metabolic; it’s a reflection of a problem of the body’s energy regulation. Neuroscientist Lisa Feldman Barrett, for example, insists that anxiety is a metabolic illness. “Energy regulation is a critical factor in mind and behavior,” she states in the 2022 Annual Review of Clinical Psychology. Thinking is not the brain’s highest purpose—energy regulation is.

In her view, the brain is a prediction machine and, in coordinating all the systems of the body, one of its primary tasks is to anticipate and manage energy requirements in an ever-changing but only partly predictable world. That rustling you heard? Based on past experience and acquired information (scary movies have their instructive value!), your brain predicted it was a snake. That guess set off a response favoring your survival: The shot of adrenaline enabled you to jump out of harm’s way.

Unpredictable environments impose metabolic costs. Uncertainty gives rise to a state of unpleasant physiologic arousal—what most people, particularly those raised in Western cultures, label “anxiety,” Feldman Barrett says, illustrating a key tenet of her theory of constructed emotion.

Addressing the metabolic disruption through metabolic means is gaining scientific steam as a way to treat anxiety. Evidence is accruing that neurobiological mechanisms linked to mental disturbances can be modulated by diet, and a growing number of researchers and clinicians are testing and prescribing dietary interventions, including the use of nutritional supplements, as stand-alone or auxiliary approaches to mental disorders.

In a paper she co-authored in Frontiers in Psychiatry, Harvard psychiatrist Umadevi Naidoo points out that among the basic metabolic disturbances underlying neurological conditions and mental illnesses are oxidative stress, insulin resistance, inflammation, and microbiome dysbiosis. The two-way channel of communication known as the gut-brain axis in particular provides a major pathway for metabolic activity to influence mental health.

One of the most significant ways the gut can influence the neural mechanisms of anxiety centers on the amygdala, instigator of the threat response. It is hyperactive in anxiety disorders. People with anxiety tend to have low levels of the gut bacteria that produce short-chain fatty acids (SCFAs), which influence amygdala activity.

Produced in the lower intestines by gut bacteria feasting on fiber-rich foods, SCFAs promote mental health by regulating gene expression and stimulating neuroplasticity in the brain. They are also metabolic protagonists. The SCFA acetate, for example, inhibits neurochemicals in the hypothalamus that increase appetite and decrease metabolism. The SCFA butyrate affects the metabolism of fats and the action of several hunger-related hormones that bind to receptors on the amygdala, influencing the stress response and anxiety.

Naidoo points to nutritional strategies that target metabolic mechanisms in anxiety. High on the lists of nutrients to consume are omega-3 fatty acids found in fatty fish. Salmon is good, she says, but fish roe and krill oil may be even better. Amount is important; doses lower than 2 grams per day tended not to be effective.

The spice turmeric, with its active ingredient curcumin, is another dietary component with proven anti-anxiety effects. It balances the gut microbial ecosystem, decreases inflammation, affects neurohormone levels, and influences gene expression in the brain.

Vitamin D is widely active in the brain, and levels of the vitamin are low in those with anxiety. Clinical studies link vitamin D supplementation with improvement in anxiety symptoms—but only in those with deficiency or insufficiency of the vitamin. That, however, encompasses a large number of people—at least one in four adults in the U.S. has a low vitamin D level.

In the future, Naidoo speculates, high-fat, low-carbohydrate ketogenic diets may be used to help control anxiety. They shift brain metabolism from glucose to more efficient ketones as a source of fuel. One major consequence is reduced oxidative stress. The fuel shift also influences neurotransmitter function and inflammatory processes.

Nutrients vs. Anxiety

Studies show a number of nutrients are associated with a low level of anxiety symptoms.

Magnesium modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, inhibiting stress response, and increases serotonin synthesis from tryptophan.

Selenium protects cells, including neurons, from damage due to oxidative stress.

Zinc regulates many biological processes; it has neuroprotective and anti-inflammatory effects and helps modulate activity of the HPA axis.

Vitamin D regulates neurotransmitter levels and secretion of brain growth factors.

Omega-3 fatty acids, among multiple roles , function as anti-inflammatory agents, influence neurotransmitter levels, increase brain growth factors, and improve microbiome balance.

Turmeric‘s active component curcumin is a polyphenol that decreases inflammation, increases serotonin, and balances the microbiome.

Prebiotics and probiotics balance the microbiome.