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“Researchers at the Rush Alzheimer’s Disease Center recently reported intriguing evidence that people with higher levels of an important nerve growth factor called BDNF tended to keep more of their cognitive functions even as amyloid built up...In fact, people who had more BDNF activity saw a 50% slower rate of cognitive decline over the study’s six years than those with lower activity.” - Alzheimer's from a New Angle (Time, February 2016)
The neuroprotein BDNF is responsible for growing new neurons and repairing broken ones. And with a growing body of scientific evidence such as the above, it's no wonder that brain derived neurotrophic factor (BDNF) is quickly becoming one of the hottest compounds in brain health.
Many people are seeking ways to increase this key protein. Right now, exercise is the most commonly known way to achieve this. But, perhaps because we all seem to want a magic bullet (or pill), others have started looking to see if supplements can boost BDNF. Unfortunately, when the science behind these products is examined more thoroughly, many of the supplements that are touted for having the ability to increase BDNF come up short.
In the name of truth, below are five of the hottest supplements claimed to help increase BNDF levels in your body, plus whether they work and, if they do, how much you need to take.
(Don't care about the details? Don't want to read all 3,600+ words? No problem. Click here to see the Supplements and BDNF Cheat Sheet.)
Coffee Fruit
The third most popular beverage in the world (behind water and tea) comes from the roasted pit or seed of a fruit called the coffee cherry. Grown on a low-lying bush, the coffee cherry resembles a cross between a cranberry and a cherry. When the fruit is harvested to make coffee, it is picked in the fields. The fleshy fruit portion is quickly discarded, and the seed (also called a pit or bean) is retained to be dried and eventually roasted and ground to make coffee.
While the antioxidant-rich fleshy fruit portion of the coffee cherry has long been coveted by people indigenous to coffee-growing regions, scientists only recently began to appreciate and quantify the health powers of this fruit.
What Do We Know About Coffee Fruit and BDNF?
Inflammation can be a driving factor for stunting the production and release of BDNF in the body. Due to their high anti-inflammatory, antioxidant characteristics, neuroscientists began to test the effects of coffee fruit and different coffee fruit components (24 different chemical fingerprints were examined) on BDNF levels in the body.
In one study, a whole coffee fruit antioxidant concentrate was given to one group of study participants, while others received the placebo (an inert powder) and yet still another group received a dose of chlorogenic acid (the major antioxidant found in coffee). Researchers found that only the people who received the whole coffee fruit antioxidant concentrate experienced significant increases in BDNF levels. And these increases were observed in less than 2 hours.
In addition to the chlorogenic acid comparison, researchers gave a fourth group of subjects green coffee bean extract powder. This comes from dried but unroasted coffee beans. Again, they saw no observed change in BDNF.
A follow-up study was then completed to look at the effect of drinking coffee on BDNF levels compared to taking whole coffee fruit antioxidant concentrate. The researchers found that coffee had a negligible effect on BDNF levels, but the whole coffee fruit antioxidant concentrate yielded a near two-fold increase in BDNF levels within 60 minutes.
How Does Coffee Fruit Increase BDNF?
The second clinical study looking at whole coffee fruit antioxidant concentrate and BDNF found that there was a specific increase of BDNF levels inside platelets. See, your body stores BDNF in your platelets (yes, the same ones in your blood used for wound healing), where it can be rapidly released as needed.
So researchers currently think that coffee fruit antioxidants increase BDNF levels by increasing DNA production of BDNF via anti-inflammatory pathways while also enhancing your body's ability to activate BDNF stored in platelets.
How Much Coffee Fruit Do You Need to Take?
Both human clinical studies used 100 milligrams (mg) of whole coffee fruit antioxidant concentrate to increase BDNF levels.
Should I Take Coffee Fruit to Increase BDNF?
Yes, with two human clinical studies showing that whole coffee fruit antioxidant concentrate (don't confuse with just freeze dried coffee fruit powder) when taken in 100mg doses can increase levels of BDNF in the body.
Coffee Fruit and BDNF Resources, Links, and Research
- Safety Studies on Products From Whole Coffee Fruit [Food and Chemical Toxicology]
- Modulatory Effect of Coffee Fruit Extract on Plasma Levels of Brain-Derived Neurotrophic Factor in Healthy Subjects [British Journal of Nutrition]
- Stimulatory Effect of Whole Coffee Fruit Concentrate Powder on Plasma Levels of Total and Exosomal Brain-Derived Neurotrophic Factor in Healthy Subjects: An Acute Within-Subject Clinical Study [Food and Nutrition Sciences]
Fish Oil
For the sake of clarity, when I say fish oil, I'm talking about the omega-3 fats EPA and DHA. Found in oily fish (and produced by algae that the fish eat), these have a myriad of powerful health-promoting effects. They also serve as the raw materials for short-lived hormones in the body called eicosanoids, which are the master regulators of inflammation in the body. This translates into improved heart health, reduced joint pain, and improved brain health, to name a few benefits.
DHA specifically is a major player in the brain. Because of its prominent role in brain health—like improving executive brain function and promoting healthy brain development in newborns—researchers have also explored if and how fish oil can improve or regulate BNDF levels.
What Do We Know About Fish Oil and BDNF?
A majority of the research related to fish oil and BDNF is preliminary or in special populations, meaning that the studies have been done in cells, test tubes, animals, or in people with conditions that fall outside of normal physiology (such as depression or schizophrenia).
Several studies in animals show that when researchers induce brain injuries, the addition of the fish omega-3 fats helps to normalize levels of BDNF in these animals.
But there are some human studies.
In a 2019 study, people received 2.2 grams (g) of fish oil per day after their first episode of schizophrenia. When measured after eight weeks and again after 26 weeks, BDNF levels were higher in the people taking fish oil. In addition, higher levels of BDNF were associated with lower depressive symptoms.
Additionally, a 2015 study found that giving 1.4 g of DHA to people who had experienced traumatic brain injuries (such as a car accident, falling from a height, or a workplace accident) led to increases in BDNF. Here again, BDNF levels were associated with fewer symptoms of depression but not with the occurrence of post-traumatic stress disorder (PTSD).
Unfortunately, currently no human studies show that taking a fish oil supplement will increase BDNF levels in healthy people.
How Does Fish Oil Increase BDNF?
Scientists believe that the fats found in fish oil work to enhance BDNF in your body in two distinct ways. The first is that these fats will turn on the cellular machinery in your body required to produce BDNF. Essentially, fish oil serves as an activator for BDNF production. The second way is by enhancing the actions of BDNF in your body. So fish oil is helping make lower levels of BDNF more effective.
How Much Fish Oil Do You Need to Take?
We're currently guessing at a dose. If we use the study completed in people with schizophrenia as our guide, you would need to take two to four capsules of fish oil a day, depending on the supplement you choose.
Should I Take a Fish Oil Supplement to Increase BDNF?
No. There are many good reasons to take a fish oil supplement (such as to support heart health, support joint health, and fight inflammation), but if you are looking to increase BDNF, a fish oil supplement should not be your first (or second) choice.
Fish Oil and BDNF Resources, Links, and Research
- Dietary Omega-3 Fatty Acids Normalize BDNF Levels, Reduce Oxidative Damage, and Counteract Learning Disability After Traumatic Brain Injury in Rats [Journal of Neurotrauma]
- Omega-3 Fatty Acids Could Alleviate the Risks of Traumatic Brain Injury – A Mini Review [Journal of Traditional and Complementary Medicine]
- An increase in plasma brain derived neurotrophic factor levels is related to n-3 polyunsaturated fatty acid efficacy in first episode schizophrenia: secondary outcome analysis of the OFFER randomized clinical trial [Psychopharmacology]
- Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial [Translational Psychiatry]
- Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia? [Current Neuropharmacology]
Curcumin
Curcumin is a compound from turmeric. It is used as a spice in cooking, as a natural coloring agent for foods and drinks, and has been used medicinally for hundreds of years. While many herbs, plants, and extracts are used in ancient and traditional medicinal practices, few have scientific backing (which doesn’t say that they don’t work, they are just not well-researched) and far fewer have undergone a handful of clinical trials in humans.
Curcumin is an exception to the rule. You will be hard pressed to find a traditional herbal extract that has been as rigorously investigated as curcumin. What is even more interesting is that the scientific interest in curcumin is only growing!
Curcumin is a potent anti-inflammatory compound that also has been shown to control stress hormones, protect the digestive system from inflammation, and even support the molecular pathways for fat loss.
Multiple human clinical trials have been run to test the safety and efficacy of (very) high dose curcumin supplementation in people as they undergo chemotherapy. As part of the increased interest and exploration surrounding curcumin, it has also been examined for its ability to increase BDNF levels in the body.
What Do We Know About Curcumin and BDNF?
A handful of animal studies highlight the fact that curcumin can beneficially impact BDNF levels. The next question that needs to be answered is whether a human supplementing with curcumin can experience meaningful increases in BDNF. At this time the answer is still unknown.
In a 2019 review looking at curcumin and BDNF published in the journal Nutrition Research, researchers analyzed four human clinical studies. They found that supplementing with curcumin lead to significant increases in BDNF.
But when you take a little closer look at the analysis, the average increase in BDNF was around 8 percent. While this is statistically significant, it likely isn't clinically significant. Rather, it is just a blip on the radar of your body's BDNF levels.
We're going to need more studies to better understand the role of curcumin in boosting BDNF, but it might be a simple as increasing the dose. Stay tuned!
How Does Curcumin Increase BDNF?
One of the current hypotheses that scientists have about curcumin's effects on BDNF centers on its anti-inflammatory properties. Oxidative stress and inflammation are potent factors that hinder your body's ability to produce BDNF. And curcumin disables one of the most potent inflammatory systems in the body (the COX-2 pathway, for those of you interested in the nitty-gritty details).
A 2017 study published in Mediators of Inflammation found that chronically stressed rats experienced a 75 percent reduction in BDNF levels. But when they were given curcumin, BDNF levels increased by up to 95 percent! This increase in BDNF was accompanied by a 263 percent reduction in activity of the COX-2 inflammatory pathway.
This study clearly highlights the relationship between fighting inflammation and supporting healthy BDNF levels.
How Much Curcumin Do You Need to Take?
The 2019 study that reported an 8 percent increase in BDNF due to curcumin supplementation included a range of dosages between 200 and 1,820 mg per day. 200 mg is not very much (it's essentially a waste of time to supplement with that little), while 1,820 mg is a high dose (2000 mg has been used for the treatment of symptoms of ulcerative colitis).
A different study published in 2014 used 500 to 750 mg of curcumin. The researchers found that these supplementation ranges didn't have an impact on BDNF levels after 12 weeks of daily use.
When you take all this research together, it is safe to conclude that you will need a least 1,000 mg of curcumin daily to have any expectation of an increase in BDNF. But even at that level, you can't be sure it will have an effect on BDNF.
Should I Take a Curcumin Supplement to Increase BDNF?
Not at this time. Like fish oil, there are many good reasons for supplementing with curcumin; however supporting BDNF levels is not one of them.
Curcumin and BDNF Resources, Links, and Research
- Effects of Curcumin on Brain-Derived Neurotrophic Factor Levels and Oxidative Damage in Obesity and Diabetes [Applied Physiology, Nutrition, and Metabolism]
- Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats [Mediators of Inflammation]
- Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials [Nutrition Research]
- Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial [Neuropeptides]
- The Impact of Age, Weight and Gender on BDNF Levels in Human Platelets and Plasma [Neurobiol Aging]
- Tumeric: Potential Health Benefits [Nutrition Today]
Cocoa
Famous for being the base for chocolate, cocoa has been a staple in the human diet for centuries. Independent of its sweet taste, cocoa was also considered healthful and even medicine due to its high concentrations of powerful flavonoid antioxidants. The specific flavonoid antioxidant theobromine has a chemical structure that makes it a cousin to caffeine and thus gives it cognitive-enhancing properties, including potentially impacting BDNF. Large population-based studies have shown that consistently consuming flavonoid-rich foods is associated with a lower rate of cognitive impairment, improved brain function, and reduced risk of dementia.
What Do We Know About Cocoa and BDNF?
Research from Sbarro Institute for Cancer Research and Molecular Medicine and the Center for Biotechnology at Temple University is starting to show that these antioxidants may have a novel use. In a 2013 study, scientists took cells that behaved as if they were inflicted with Alzheimer's disease and treated them with antioxidants extracted from cocoa. These antioxidants turned on the cells' protective mechanism by activating the BDNF survival pathway.
Unlike some of the other compounds we discussed, clinical trials in humans show that consuming cocoa can increase BDNF levels. In a study published in Nutrition and Healthy Aging, a daily cocoa drink containing 494 mg of flavanols lead to significant increases in BDNF levels over the course of 12 weeks.
An interesting side note to this study is that the researchers also tested brain function. They found that eating a lot of fruits and vegetables each day supercharged the effects of the flavonol cocoa drink and lead to even better scores on the brain function tests.
It should be noted that a 2016 study completed at the University of Brussels found that a one-time dose of a cocoa supplement containing 903 mg of flavonols taken after exercise or at rest had no effects on BDNF levels. It did, however, increase blood flow to the brain.
How Does Cocoa Increase BDNF?
Scientists know from animal studies that the antioxidants in cocoa can act in two specific areas of the brain (the lateral ventricles and hippocampus dentate gyrus) to increase the production of genes that make BDNF. If you think of your brain as a factory, this would be the equivalent of increasing the number of machines in your factory needed to produce BDNF.
Other research shows that these antioxidants activate the "BDNF Survival Pathway". This is a specific sequence of events where BDNF is called upon to help with the repair and rescue of neurons from injury (for example, cellular damage that occurs via something like Alzheimer's disease progression).
One other potential way that cocoa increases BDNF levels is by activating the CaMKII/CREB/BDNF pathway in the brain. That sounds like a made-up string of letters, but it isn't. This pathway is important for both learning how to complete physical tasks (i.e. motor learning) as well as multi-tasking (i.e. working memory).
How Much Cocoa Do You Need to Take?
Based on the findings of the high cocoa beverage study, you would need to have about two tablespoons of unsweetened cocoa powder (this stuff or this) each day. This will deliver approximately 500 mg of flavanol antioxidants.
It is important to remember that using cocoa to boost BDNF levels is a long-term play. Remember, the Belgian researchers from the University of Brussels found that a one-time dose of almost four tablespoons of cocoa powder had no effect on BDNF levels.
Should I Take Cocoa to Increase BDNF?
Yes, consuming 2 Tbsp of unsweetened cocoa powder (or a more concentrated version of cocoa powder) so that you are getting 500mg of cocoa flavanol antioxidants on a daily basis is a strategy for increasing BDNF levels. Please remember that this needs to be a daily occurrence and just doing it once will not help.
Cocoa and BDNF Resources, Links, and Research
- The relevance of theobromine for the beneficial effects of cocoa consumption [Frontiers in Pharmacology]
- Enhancing Human Cognition with Cocoa Flavonoids [Frontiers in Nutrition]
- Cocoa Powder Triggers Neuroprotective and Preventive Effects in a Human Alzheimer's Disease Model by Modulating BDNF Signaling Pathway [Journal of Cellular Biochemistry]
- Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats [Nutrients]
- A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subven-tricular zone and hippocampus of adult mouse brain [Journal of Alzheimer's Disease Research]
- High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: two randomized, controlled trials. [Nutrition and Healthy Aging]
- Acute Cocoa Flavanol Improves Cerebral Oxygenation Without Enhancing Executive Function at Rest or After Exercise [Applied Physiology, Nutrition, and Metabolism]
Lutein
Lutein is a naturally occurring antioxidant that's part of the carotenoid family. This is the group of antioxidants that gives fruits, vegetables, plants, and egg yolks their yellow-orange color. You've probably heard of beta-carotene. That's the antioxidant that makes carrots and pumpkins orange. Lutein is beta-carotene's cousin.
Lutein is most well known for its ability to support eye health. Consuming adequate levels of lutein significantly reduces your risk for the eye disease macular degeneration. Lutein also concentrates in the back of your eye (the retina, to be exact) and filters out blue light, which is known for stimulating hyperactivity and disrupting natural sleep rhythms.
More recently scientist began exploring further benefits of lutein such as how it provides UV protection to our skin cells and can improve brain function. As you can see, there is tremendous potential for lutein to improve your life, but for now, we want to focus solely on the impact that lutein has on BDNF.
What Do We Know About Lutein and BDNF?
Lutein and BDNF is an exciting and growing area of research to watch. There is currently one long-term study in humans showing that daily supplementation with lutein, zeaxanthin, and the zeaxanthin isomer meso-zeaxanthin (the latter two are essentially lutein's antioxidant siblings) leads to increases in BDNF after six months. It's interesting to note that the increases in lutein levels in the blood over the course of the study were also related to increases in sustained attention and verbal memory.
A handful of animal studies show that lutein supports BDNF levels and BDNF production. One study to note shows that in a model for diabetes, supplementing with lutein can prevent depletion in BDNF in the retina (and thus potentially the brain).
How Does Lutein Increase BDNF?
The current thinking is that leutin reduces neuro-inflammation. We know that inflammation decreases BDNF and that lutein is a powerful antioxidant that is preferentially concentrated in our eyes and brains. As our body's stores of lutein increase, it gives us greater capacity to fight inflammation and thus allow our body to produce the BDNF it needs without hindrance.
Other research in animals has shown that when exercise is combined with lutein supplementation, it increases your body's ability to produce BDNF at the DNA level.
These two studies show that lutein likely works to increase BDNF via at least two distinct ways in our bodies:
- Taking the brakes off of our body's ability to produce BDNF by fighting inflammation.
- Accelerating BDNF production by stimulating action at the DNA level.
How Much Lutein Do You Need to Take?
The six-month study with lutein and zeaxanthin provided study subjects with a variety of dosages. The lowest dose was 13 mg. This yielded significant increases in BDNF after six months. A previous study completed at Tufts University found that 10 mg of lutein daily improved scores on several cognitive function tests. BDNF was not measured, but this suggests that 10 mg might also be an effective dose.
Should I Take Lutein to Increase BDNF?
Yes, lutein/zeaxanthin has a variety of health benefits and daily intake of 13mg will increase BDNF levels after several months. As with cocoa flavanols, this needs to be a daily regimen - don't take one dose and expect to experience a difference.
Lutein and BDNF Resources, Links, and Research
- Neuroprotective Effects of Lutein in the Retina [Current Pharmaceutical Design]
- Regular Exercise Training with Lutein/zeaxanthin Isomers Regulates Brain Transcription Factors and Neurotrophic and Synaptic Proteins in Rats (P06-020-19) [Current Developments in Nutrition]
- Neurodegenerative Influence of Oxidative Stress in the Retina of a Murine Model of Diabetes [Diabetologia]
- Effects of Macular Xanthophyll Supplementation on Brain-Derived Neurotrophic Factor, Pro-Inflammatory Cytokines, and Cognitive Performance [Physiology & Behavior]
- Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women [Nutritional Neuroscience]
Supplements that Increase Brain Derived Neurotrophic Factor (BDNF) Cheat Sheet
I know some people don't want to read 3,600+ words on supplements and BDNF (totally cool!), so I created a cheat sheet for you.
Coffee Fruit Antioxidants
- Shown to increase BDNF in healthy humans: yes
- How much to take: 100 mg
- How fast does It work: 60 minutes
Fish Oil
- Shown to increase BDNF in healthy humans: no
- How much to take: n/a
- How fast does it work: n/a
Curcumin
- Shown to increase BDNF in healthy humans: no
- How much to take: n/a
- How fast does it work: n/a
Cocoa
- Shown to increase BDNF in healthy humans: yes
- How much to take: 500 mg
- How fast does it work: 12 weeks
Lutein
- Shown to increase BDNF in healthy humans: yes
- How much to take: 13 mg
- How fast does it work: 6 months
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April 18, 2021
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