Tens of thousands of supplements flood the market today. Sadly, many of them do little more than lighten your wallet, and a few can be downright bad for you.
Others — such as fish oil, vitamin D, creatine, probiotics, greens powders, and the humble multivitamin — can improve our health, athletic performance, and body composition.
And then there’s another group of supplements that offer equally important (and research-supported) benefits — while remaining largely unknown and little used.
Eager to learn more about these, I spent a few hours over at Examine.com, an expertly curated site that compiles and analyzes the latest research about hundreds of supplements and foods, along with other questions related to nutrition and health.
The database alone refers to more than 50,000 research papers. Editors painstakingly sift and sort the information to make it easier to understand. The result is a highly valuable resource to anyone who cares about nutrition and health.
Though I consider myself pretty knowledgeable, I came away from perusing the site with new insights about some amazing — but lesser known — supplements that I simply had to share.
Surprising Supplement #1: Curcumin
Curcumin is the yellow pigment in turmeric and curry spice, and it’s been studied for decades because of its many potential health benefits.
Because curcumin reduces inflammation, especially if taken long-term, it also decreases pain, particularly post-operative and arthritic pain.
In fact, long-term curcumin supplementation decreases symptoms of osteoarthritis by more than half. When elderly and middle-aged patients with osteoarthritis took curcumin, it drastically improved their comfort and performance, allowing them to lead more active lives.
Curcumin also helps with general day-to-day pain – and the relief provided by 400 to 500 mg of curcumin seems comparable to taking 2000 mg of acetaminophen (Tylenol).
Curcumin can help reduce the pain associated with other diseases, such as ulcerative colitis and nephritis, limiting the inflammation and improving organ function. And perhaps because of its effects on inflammation, curcumin may also slow brain aging and cognitive decline.
Besides reducing inflammation, taking curcumin for longer periods decreases various markers of oxidation, such as C-reactive protein or lipid peroxidation.
Free radicals (cells that have become damaged during oxidation) lack critical molecules. In trying to repair themselves they sometimes go on a rampage in our bodies, ultimately injuring more cells by corrupting their DNA. This can lead to disease.
Our bodies naturally contain antioxidant enzymes to help protect us – namely, super-oxide dismutase (SOD), glutathione, and catalase. These powerful enzymes are our main defense against runaway oxidation.
Interestingly, not only is curcumin a strong anti-inflammatory and antioxidant by itself, it also significantly increases levels of these inherent bodily enzymes, further bolstering our defenses.
Because of this, curcumin supplementation can protect DNA from damage – even when someone is exposed to dangerous compounds, such as arsenic!
Curcumin also seems to have anti-cancer benefits. This is because it can start a process called autophagy.
Autophagy is the selective destruction of damaged cellular tissue. Think of it as cellular housekeeping – cleaning up damaged debris and preventing damaged cells from accumulating.
Autophagy helps to isolate damaged organelles, allow appropriate cell differentiation, and promote the death of cancerous cells. In other words, it puts some of the bad guys in solitary, separates those who need to be separated, and kills off others.
People whose diets are high in curcumin are less at risk for colorectal cancer, prostate cancer, and breast cancer.
And if you’re already suffering from cancer, curcumin might even make chemotherapy more effective and protect healthy cells from radiation therapy. Not too shabby.
Safety and dosing
The commonly recommended dose for general health purposes is around 500 mg of curcumin daily. Research suggests that doses of up to 8-12 grams per day are safe. The main reported side effect is some gastrointestinal discomfort.
However, curcumin by itself is poorly absorbed. So to benefit from it, you’ll need a supplement with enhanced bioavailability.
Methods to improve bioavailability include added black pepper extract (piperine), mixing with phosphatidylcholine (phytosomes), or taking a curcumin nanoparticle product. Check labels to ensure you’re getting a product that will actually be absorbed.
Curcumin is fat-soluble, so it should be taken with a meal or other fat source (such as fish oil) to help boost absorption further.
Surprising Supplement #2: Berberine
Berberine is a compound found in many plants, including Oregon grape, barberry, and goldenseal, among others.
Much like curcumin, berberine is yellow-colored – so strongly colored, in fact, that it was once used to dye wool, leather and wood.
Berberine’s magic powers include anti-inflammatory effects, lipid-lowering effects, and most of all, incredibly powerful anti-diabetic effects. Many of these are due to berberine’s activation of AMPK, a potent enzyme that is key to maintaining the energy balance in our cells and protecting their growth and function.
Berberine also has some anti-fungal and anti-biotic properties.
But let’s look at berberine’s most potent benefits.
Blood sugar control
Berberine’s anti-diabetic properties are well-established. In fact, berberine is every bit as powerful as a pharmaceutical drug. Not many supplements can boast that kind of effectiveness.
Taking 500 mg of berberine 3 times per day (1500 mg total) appears to improve glucose control and other markers of type 2 diabetes just as well as taking 1500 mg of the diabetes drug Metformin.
Not only that, but when taken together, Metformin and berberine seem to work synergistically for even better glucose control.
But diabetics are not the only people who could benefit from taking berberine. It might also protect against metabolic syndrome, since it reduces blood glucose, body fat, triglycerides, and cholesterol.
Berberine seems to work through multiple pathways.
First, it improves muscle insulin sensitivity, and promotes blood glucose and fatty acid uptake into muscle cells.
It also seems to prompt the liver to decrease glycolysis, and down-regulate the high level of free fatty acids in the blood that occur due to poor body composition – thus decreasing insulin resistance.
A series of three trials, using around 1 gram of berberine daily for 1-3 months in people with metabolic syndrome or type 2 diabetes showed that their fasting blood glucose decreased by 17-26%, and their HbA1C levels by 12-18%. (HbA1C is a measure of blood glucose control over time.)
These are remarkable improvements, easily comparable to those obtained by taking diabetes drugs.
Reduced blood lipids
Berberine can also reduce blood lipids. This means it might protect against heart disease.
A meta-analysis of berberine supplementation in diabetics found that on average it lowered triglycerides by 42 mg/dL, and both total cholesterol and LDL-cholesterol went down, on average by 22 mg/dL. Those are serious reductions!
Not only that, but when it comes to reducing lipids, berberine seems to work differently than statins – currently the most commonly prescribed drug for this purpose. So theoretically, the two substances could work synergistically to lower blood lipids more efficiently and effectively than either alone.
Safety and dosing
Most trials of berberine have adopted a dose of 1-2 g per day, divided into 3 or 4 servings. Larger doses have been well tolerated, but not necessarily more beneficial.
Other than mild gastrointestinal distress if large doses are taken at once – and the chance that it might inhibit muscle growth – berberine appears to have few side effects.
Note of caution
The AMPK activation effects of berberine are incredible at improving blood glucose control and reducing blood lipids, but this comes at a mild cost: The increase in AMPK might actually inhibit muscle growth.
This unwanted side-effect might be somewhat or mostly offset by vigorous resistance training and anaerobic exercise. But so far, research is lacking, so that is mostly an educated guess.
Finally, berberine is known to interact with enzymes used in pharmaceutical drug metabolism. This means it can interfere with appropriate metabolism of prescription medications, such as certain anti-biotics, that could lead to serious cardiotoxicity. Check with your doctor before supplementing.
Surprising Supplement #3: Spirulina
Spirulina is a blue-green mixture of algae species. It contains bioactive compounds (including phycocyanobilin) that confer exceptional health benefits. In particular, spirulina seems to inhibit NADPH oxidase, a pro-oxidation compound. So it helps protect us against free radicals and the damage they can cause to healthy cells.
Granted, the data on many of spirulina’s reputed benefits is limited and needs to be replicated before we can judge with absolute confidence. But preliminary evidence is compelling.
Blood lipid protection
Several studies have shown that spirulina supplementation in both humans and animals lowers lipid peroxidation levels (a marker of damaged blood lipids) by around 15% on average.
A number of studies on people with metabolic syndrome or other diseases involving high triglycerides have shown that supplementing with spirulina can reduce triglyceride levels by about 10-15%.
Effects that need more research
- Allergy control. One study showed that 2 g of spirulina daily for 6 months was associated with significantly reduced symptoms of nasal allergies.
- Blood pressure reduction. A few studies have shown that 6 weeks of supplementation reduced blood pressure in people without hypertension by 11 points for systolic pressure (the top number) and 6 points for diastolic (the bottom number). Those are large changes.
- Power output increase. In a lone study, power output during exercise increased by 20-30%, where a placebo failed to produce any increase. The effect was stronger in untrained individuals, and weaker in trained athletes.
- Immune system up-regulation. One study showed that natural killer cell content and activity both increased significantly when subjects took spirulina. This suggests that spirulina might offer strong anti-tumor benefits.
- Liver enzyme and liver fat reduction. While based on case studies and rat data, this preliminary evidence seems to indicate that spirulina may improve liver health in those with liver damage.
Safety and dosing
Spirulina received a Class A safety rating by the United States Pharmacopoeia. Currently, there is no evidence to suggest any harm associated with its intake.
It should be noted, however, that other non-spirulina blue-green algae could contaminate spirulina supplements and potentially produce toxic metabolites. So if you choose to supplement, do look for a reliable source.
Spirulina is generally taken at 1-3 g per day, often in divided doses.
Surprising Supplement #4: Rhodiola rosea
Rhodiola rosea may sound like the name of a character in a kids’ book. But it’s actually an adaptogenic herb that grows in cold climates, such as the Arctic, and other mountainous regions of the world.
An adaptogenic compound is one that can soften the negative effects of stress, even when the perceived stress remains. (To learn more about stress, see Good Stress, Bad Stress: Finding Your Sweet Spot.)
Rhodiola is an adaptogen that has a strong track record of decreasing fatigue and exhaustion in prolonged stressful situations. (Including situations like my own: living in the same house with an infant and a toddler.)
Decreased fatigue; improved well-being
The research on rhodiola’s ability to decrease fatigue and improve well-being is strong, and has been repeatedly demonstrated.
A meta-analysis of 5 studies found that compared to students taking a placebo, students who took rhodiola had less cognitive fatigue, better motor skills, and made fewer errors on tasks. They also stayed more focused, reacted more quickly, and felt generally happier.
In fact, in one of those studies, the students taking rhodiola scored 8.4% higher on their exams than the placebo group. That’s a pretty big advantage!
Beyond the academic setting, rhodiola supplementation has also drastically reduced total fatigue and increased the capacity for mental work and overall sense of well-being in military cadets performing night duties.
Finally, in a study on healthy physicians, rhodiola supplementation significantly decreased fatigue and improved performance on work-related tasks by ~20%.
Rhodiola seems to make us smarter by reducing fatigue, not for any independent reason. Where mental fatigue is not a problem, it’s not clear if rhodiola does much to improve cognition.
Having said that, the cognitive effects of reducing fatigue appear quite strong.
Effects that need more research
Like spirulina, rhodiola appears to offer additional benefits. But research remains in the preliminary stages, so we can’t be certain.
However, here are a few of its suspected advantages:
- Reduces depression. In the sole relevant study, supplementation with rhodiola decreased depressive symptoms by up to 50%. One study is not enough to go on, but the result is significant, even so.
- Increases lifespan. Worm and fly research with rhodiola has shown increases in lifespan by 10-24%. While this is intriguing, it is certainly not clear that this benefit would extend to humans. A lot of other life-extension therapies that have worked in worms and flies have failed to carry over to humans.
Safety and dosage
Human trials supplementing with rhodiola have not found any clinically relevant side effects. However, it could interact with some pharmaceutical drugs, so if you wish to supplement, be sure to discuss with your doctor first.
Rhodiola rosea extract should be 3% rosavins and 1% salidroside. Normal dosage usually ranges from 250-680 mg.
In addition, rhodiola has a bell curve response, meaning once you exceed that 680 mg threshold, the effectiveness of the supplement actually decreases. There’s no point in taking more.
Surprising Supplement #5: Betaine
Betaines naturally occur in many plants to protect cells from dehydration. Sugar beets, quinoa, and spinach are three of the best food sources of betaine.
Improved strength and power
A moderate amount of research suggests that giving resistance-trained subjects 2.5 g of betaine per day may increase the number of reps they can complete, which in turn contributes to increased strength. While the improvements in the studies were relatively minor, even minor improvements can be significant in trained athletes, who are looking for every edge they can get.
Some research also indicates that betaine can lead to improvements in peak and average power output.
Other research suggests that taking betaine can significantly increase bench throw power, isometric bench press force, vertical jump power, and overall peak power. But other studies fail to find this benefit at a similar or lower dose.
The research on betaine and endurance is still in its infancy. But supplementing with betaine has allowed some subjects to maintain high-speed sprints for longer periods.
Note, however, that betaine supplementation doesn’t seem to improve performance in long-distance endurance sports. So it probably won’t help you in a marathon.
Improved body composition
Long-term betaine supplementation can improve body composition as well.
Subjects who took 2.5 g of betaine per day for six weeks while on a structured training program showed increased upper arm muscle mass. Meanwhile, they gained 2.4 lbs of lean body mass, and lost 2.9 lbs of body fat, which improved body composition by over three per cent. The placebo group showed almost no changes in those areas.
However, this was the first study to show such results; other research in non-exercising individuals showed no improvements in body composition.
Effects on cardiovascular health
Betaine supplementation consistently reduces homocysteine levels. This is a good thing, because high levels of homocysteine are linked to heart disease.
At doses of 6 g per day, betaine can actually increase levels of LDL cholesterol and triglycerides in healthy subjects. But doses of 4 g per day had no effect on blood lipids. So the research here is inconclusive overall.
Safety and dosage
The generally recommended dose is 2.5 g per day. Lower than that and you won’t get any benefits, and too much higher than that (up to 6 g per day) and you could run into trouble – for example, increased blood lipids.
Apart from that, no serious side effects have been reported – but again, the research is still in its early stages.
Surprising Supplement Bonus: Beetroot juice and nitrates
Nitrates occur naturally in many foods, with beets and spinach being two of the richest sources. This high nitrate content may help explain why beetroot juice shows some positive effects on human performance.
Why do nitrites improve performance? Well, nitric oxide seems to reduce our oxygen needs during exercise. A decreased need for oxygen reduces our ATP turnover, and since ATP is the key energy source during exercise, we can perform longer, harder and more efficiently.
Research comparing beetroot juice with its naturally occurring nitrates, vs. beetroot juice with its nitrates removed, found that the nitrate content of the juice is what leads to the positive benefits.
Another big source of nitrates in some diets is processed meat. Nitrates are added to processed meats as a preservative to prevent bacterial growth. These nitrates are then converted into nitrites by the body.
When eaten in fruits and vegetables, nitrates seem to provide health benefits, especially to the heart. However, nitrates from processed meat are linked to increased risk of certain cancers, as well as heart disease and diabetes.
It’s not clear that it’s the the nitrates in processed meats themselves that cause these negative effects, especially since nitrate-rich fruits and vegetables are linked with lower risks of these conditions. So for now, it’s best to limit processed meat – while enjoying plenty of vegetables.
Several studies have shown that nitrate supplementation, mainly from beetroot juice, can improve endurance capacity and time trial performance. Time-to-exhaustion has been improved by 15%. And running velocity has been improved by 5%.
Eating beets can also improve muscle recovery between sets of resistance exercise, reducing exhaustion and restoring oxygen recovery of muscle tissue (via our mitochondria).
Finally, beetroot consumption has improved power output in trained cyclists, leading to improved speed and faster times in time trial tests.
But note that these improvements may be more obvious in moderately trained people versus elite athletes.
To learn more about how beets and beetroot juice can affect performance, see Precision Nutrition’s Research Review: Can beets help you run faster?
Lower blood pressure
Over sixteen high-quality, randomized, placebo-controlled trials (the strongest kind) have been conducted on beetroots/nitrates and effects on blood pressure.
Overall the data show that on average beetroot juice consumption lowers systolic blood pressure (the top number) by 4.4 points, and diastolic (the bottom number) by 1.1 points.
Safety and dosage
Almost all trials using beetroot juice have asked subjects to drink 500 ml for several days prior to testing. Smaller doses or shorter time frames (eg. one dose immediately prior to event) show less consistent benefits. Unless you are allergic, there’s probably no risk to drinking 500 ml of beet juice per day.
What you can do
Surprised by the benefits associated with these lesser-known supplements? I was. And I’m glad that research is ongoing so we can keep learning more.
For now, despite their benefits, most of us probably don’t need to take any of these supplements regularly.
Sure, curcumin and/ or spirulina may offer some long-term benefit, especially if you have specific health risks.
However the performance benefits of betaine and beetroot juice may only be relevant for competitive athletes.
While berberine and rhodiola should be used in very specific situations – addressed above – instead of indiscriminately.
And remember: Just because you can buy supplements over the counter doesn’t mean they’re always safe for you.
So, before you consider adding these to your routine, be sure to discuss with your doctor and/or pharmacist. This can help you prevent dangerous drug and supplement interactions.
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