Curcumin and Brain health (SQ-107)

Like all other body systems, your brain changes with age. There are more memory slips. You have trouble paying attention, recalling names or even learning new things. You may even find it difficult to multi-task. The decline in these cognitive abilities is common as you get older.

However, plenty of studies suggest that you can do a lot to support your brain health and slow-down age-related neuro-degeneration.  Quitting smoking, getting enough physical exercise, eating a healthy diet, reading and trying word puzzles for mental stimulation are some things you can do to keep your brain healthy and well-functioning for a longer time. In fact, engaging in a new and stimulating activity is great for maintaining as well as building new cognitive skills, according to Harvard Health.

Evidence is also building on how plant-based compounds like curcumin and resveratrol  can support your brain health and may slow-down processes that cause degeneration in the brain and decline in cognitive capabilities. This is mostly due to their role in reducing inflammation, which is one of the main forces that drive cognitive dysfunction in old age.

Curcumin is one of the biologically active compounds in the spice turmeric. The polyphenol gives turmeric its intense gold-yellow color and may be at the centre of the question as to why turmeric offers an array of impressive health benefits.

While you may think of curcumin or turmeric as the latest fad in the world of superfoods, it is certainly not new to the world of functional medicine. It is considered a miracle spice in both Ayurvedic and traditional Chinese medicine, where it has been traditionally used for literally thousands of years as a natural treatment for various chronic health conditions including joint pain, liver disorders and poor digestive health.

There has been a lot of research on the compound that suggest its usefulness in a number of conditions such as heart disease, endothelial dysfunction, type 2 diabetes and insulin resistance, radiation damage and arthritis.

Can curcumin really protect your brain against the effects of aging? Let’s explore the science on curcumin and brain health.

Curcumin’s antioxidant and anti-inflammatory potential

The reason why curcumin is used in dealing with various health issues is its ability to reduce oxidative damage and inflammation in the body.

You may be hearing a lot about ‘inflammation’. There is no dearth of information on how you can naturally control inflammation through lifestyle, diet and antioxidant supplements. All this hype is justified, as long-standing inflammation in the body has been strongly implicated in almost every chronic disease.

In a normal scenario, inflammation is not a bad thing. Short-term inflammation is a healthy and even necessary response to fight and recover from infections and injuries. It protects, repairs and heals the body.

Chronic inflammation, on the other hand, is what you should be wary of. It pushes the body to age early, causes organ damage and results in the onset of health issues that typically affect you in old age.

It begins when excessive generation of free radicals results in oxidative damage in cells and tissues. Your tissues need oxygen for their energy requirements. This process also causes production of free radicals - molecules with unpaired electrons - which damage cells. External factors such as continuous exposure to toxins and chemicals, smoking or struggling with chronic infections or illness are another source of free radicals.

How systemic inflammation affects brain health

Oxidative damage and inflammation are detrimental to all your tissues and organs. But your brain is particularly vulnerable to the damage caused by chronic inflammation. While it is only 2% of the total body weight, your brain consumes more than 20% of your body’s oxygen reserves to support its intensive energy demands. It requires a high level of energy to help nerve cells (neurons) to fire signals to communicate with each other, to maintain the health of brain cells and to support a myriad of processes that take place in the brain. But so much oxygen consumption also translates into increased susceptibility of brain cells to oxidative damage and inflammation.

Chronic inflammation of the brain affects your brain health in more ways than one, such as:

• Reduces energy production in the brain, which slows down the electric impulses that help neurons communicate with each other
• Impairs your brain’s ability to regenerate brain cells (brain plasticity or neuro-plasticity). Your brain continuously changes its function and structure to keep up with internal or external changes.
• Impairs the integrity of the blood-brain barrier (BBB), making it permeable to systemic toxins and inflammatory chemicals. BBB permeability is an important piece of the puzzle in conditions such as Alzheimer’s disease. [1]
• Reduces the levels of important neurotransmitters (brain chemicals) such as serotonin. This can cause depression, anxiety and memory issues.

Chronic inflammation in the brain gives rise to symptoms like brain fog, depression, anxiety, memory loss and fatigue. It can also lead to serious neurological diseases such as Alzheimer’s disease and stroke.

Can curcumin help in any of these processes? Does it target these problem areas?

Curcumin has a strong ability to fight oxidative stress and inflammation. Preclinical and small-scale clinical trials are finding that curcumin may protect the brain from neuro-degeneration, reduce depressive symptoms and induce brain plasticity.

Curcumin in Alzheimer’s disease

Abnormal inflammatory responses in the brain are strongly linked to brain diseases and psychiatric disorders such as Alzheimer disease, Parkinson disease and depression. Neuroinflammation may be caused by trauma, exposure to heavy metals and infections.

Alzheimer’s disease is a leading cause of dementia and it affects a person’s thinking, learning, memory, reasoning, decision-making and behavior. People with Alzheimer’s disease have increased accumulation of amyloid plaques between nerve cells and neurofibrillary tangles within the nerve cells of their brain.

Amyloid plaques are clumps or aggregates of abnormal protein called beta-amyloid that destroy connections between neurons and cause loss of neuron function and cell death. An article in National Institute on Aging explains in detail how Alzheimer’s disease affects your brain health.

And neurofibrillary tangles are clumps of damaged tau protein that get collected within the nerve cells. In healthy, undamaged brain cells, you need tau proteins to stabilize microtubules, which are internal structures of the brain cells. Microtubules support the function of brain cells. Inflammatory changes in the brain make tau proteins detach from microtubules, come out and stick to each other, forming neurofibrillary tangles. Hard amyloid plaques and twisted tangles degrade neurons and interferes in their ability to fire signals. All this impacts memory and cognitive functions, resulting in the symptoms of Alzheimer’s disease.

Abnormal build-up of aggregated proteins and systemic inflammation activate microglial cells, specialized immune cells in your brain that identify and attack amyloid plaques. During this fight, inflammatory chemicals such as cytokines are also released. In this way, activation of microglial cells contributes to more inflammation and increased deposits of amyloid plaques in the brain.  

A growing body of evidence suggests that curcumin can cross the blood-brain barrier and prevent the formation of amyloid plaques. It may even help break-down these brain-damaging plaques. In addition, curcumin regulates the aggressive activity of microglial cells, known to contribute to inflammation. Curcumin also helps in the clearance of tangles of tau proteins.

This 2018 article highlights the beneficial effects of curcumin on Alzheimer’s and reports that “Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reaches brain cells, and protects neurons from various toxic insults of aging and Aβ in humans.” [2]

A 2017 research summarized curcumin’s mode of action in Alzheimer's Disease. It reported that besides being an antioxidant, curcumin prevents the formation of amyloid-β plaques and helps in their break-down, clears tangles of tau protein, binds to heavy metals like copper, lowers cholesterol and changes microglial activity. The review concluded that “curcumin has the potential to be more efficacious than current treatments. However, its usefulness as a therapeutic agent may be hindered by its low bioavailability. If the challenge of low bioavailability is overcome, curcumin-based medications for AD may be in the horizon.” [3]

(The question of low bioavailability is answered by liposomal technology. To understand more about liposomal technology, please click here .)

Since curcumin can cross the blood-brain-barrier and protects brain cells from inflammation, this increases blood flow to the brain. This is yet another mechanisms that helps in improving memory and cognition.

Promising animal studies show that curcumin also increases the production and activation of BDNF (brain-derived neurotrophic factor). [4] BDNF is a hormone that plays an important role in the growth, maintenance and survival of neurons. It stimulates the production of new neurons and helps create new neural connections.

This increases neuro-plasticity, your brain’s ability to rewire itself. Healthy levels of BDNF help you learn faster, improve your memory and allows your brain to age more slowly. Exercise, sound sleep and meditation increases BDNF levels. So does polyphenols such as curcumin.

Curcumin in depression

Can neuro inflammation also cause depression, anxiety and other psychiatric disorders?

There is scientific evidence that high levels of inflammation in the brain will lead to changes that cause depression. A study in 2017 gives insights into how inflammation may increase one’s risk of depression. The researchers found that inflammation reduces the birth of new cells while speeding up death in existing brain cells. [5]

Recently, a group of Japanese researchers also found that repeated stress activates microglia and releases cytokines and other inflammatory chemicals, causing neural inflammation. This affects the function of brain cells in certain areas of the brain, causing depressive behaviour. [6]

What is the role of curcumin in depression?

Patients suffering from depression and mood disorders have increased levels of inflammatory cytokines and activated microglia (immune cells associated with inflammation).  What’s more, people with chronic health conditions are more vulnerable to depressive symptoms.  Systemic inflammation also disrupts the production of serotonin, dopamine and glutamate. These brain hormones are strongly involved in mood, behaviour and anxiety disorders.

Curcumin is a strong antioxidant and anti-inflammatory. It blocks the production and activity of certain enzymes and cytokines that trigger inflammation. Most importantly, curcumin inhibits Nuclear factor-κB, a very important signalling pathway involved in inflammation and pain.

Many studies show that curcumin may be effective in treating patients with depression and anxiety. [7] [8] [9] Long term use of anti-depressants will cause side-effects such as weight gain, blurred vision, insomnia, sexual dysfunction and fatigue. Evidence is growing that curcumin can produce anti-depressant effects without causing any unpleasant side effects.  

A randomized, double-blind, placebo-controlled trial studied the effects of curcumin supplementation in reducing depression when used with antidepressants. It showed that curcumin can increase the efficacy of antidepressant treatments.

Just six weeks of supplementing with curcumin was shown to reduce depressive behaviour and decrease levels of inflammatory markers such as cytokines and salivary cortisol, while increasing the levels of brain-derived neurotrophic factor. These findings suggest that curcumin supplements have the potential to “reverse the development of depression and enhance the outcome of antidepressant treatments in major depressive disorder” [10]

A quick summary of how curcumin supports brain health

Curcumin prevents neuro-degeneration and cognitive decline by:

• Reducing inflammation in the brain and limiting oxidative damage
• Reducing the formation of amyloid-beta plaques, that cause dysfunction and death in brain cells
• Clearing tangles of distorted tau proteins, that destroy neurons
• Increasing blood flow to the brain
• Increasing the levels of BDNF, a hormone that increases your brain’s ability to make new neurons and form new neural pathways

What most studies have found is that curcumin is most effective in people with mild cognitive impairment versus those with an advanced stage of Alzheimer’s. In other words, taking curcumin supplements is much more effective when taken before the condition worsens.  

We need more large-scale clinical trials to uphold curcumin’s role in Alzheimer’s and depression. But there is a reason why many clinical studies – that have investigated the role of curcumin in neuro-degenerative disorders and other inflammatory conditions – have met with limited success.  It is because curcumin is not highly available to the cells, due to its poor solubility and fast metabolism.

However, liposomal curcumin formulations  have found to be extremely effective in overcoming this barrier of poor absorption and low bio-availability in cells.

There are many things you can do to keep your brain healthy and prevent premature degeneration. We have already discussed how dancing is good for your brain  and protects your brain from aging, and using a natural, plant-based, anti-inflammatory like curcumin is a great addition to these efforts.

Since it reduces overall inflammation in the body, a high-quality curcumin supplement would be helpful in other conditions where oxidative damage and inflammation play an important role. For example, curcumin has been found to be beneficial in reducing your risk of heart disease, reducing joint pain and improving quality of life in people with rheumatoid arthritis. It has also been shown to manage symptoms in people with irritable bowel syndrome.

References:

1. Varatharaj A et al. The blood-brain barrier in systemic inflammation. Brain Behav. Immun. 2017.
2. Reddy et al. Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease. J Alzheimers Dis. 2018
3. Tang et al. The Mechanisms of Action of Curcumin in Alzheimer's Disease. J Alzheimers Dis. 2017
4. Wu et al. Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders. Biochim Biophys Acta. 2015
5. Borsini, A et al. Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms. International Journal of Neuropsychopharmacology. 2017
6. Nie et al. The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation. Neuron, 2018.
7. Sanmukhani J et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014
8. Lopresti AL, Maes M, Maker GL, et al. Curcumin for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Dis. 2014.  
9. Ng QX et al. Clinical Use of Curcumin in Depression: A Meta-Analysis. J Am Med Dir Assoc. 2017
10. Yu JJ et al. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol. 2015

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