Antioxidants versus Cellular Protectors
There is a generally accepted idea in the marketplace that good antioxidants come from fruits and vegetables and that these natural antioxidants scavenge free radicals in the body that causes damage, disease and aging. Fruit and vegetable concentrated extracts are sold as supplements to counteract poor diets that don't include enough fresh fruits and vegetables. These are mainly marketed as "rich in antioxidants which will scavenge free radicals." Demonstrations of free radical scavenging in test tube measurements by antioxidants and animal and cell culture experiments of imposed oxidative stress proving damage to cells, has contributed to this generally accepted idea. Thus the universal idea (and marketing concept) evolved that since free radicals produce damage and antioxidants scavenge free radicals, antioxidants must be health protective because they quench free radicals. Thus, it was presupposed that the more antioxidants one could pack into cells and tissues, the greater would be the resistance to pathology caused by free radicals.
This subsequently primed the development and implementation of scientific measurements of the capacity of both pure plant chemicals and plant extract samples to quench free radicals in test tube studies. Such studies have flooded the scientific literature for the past two decades. In these experiments, different radicals produced in vitro are reacted with molecules or chemicals present in the plant sample under scrutiny. One can then measure either the extent to which radicals are ‘quenched’ or the kinetics of the oxidation of a reported molecule, as altered by the ‘antioxidant’ under study. By such methods, both plant extracts and thousands of phytochemicals have been shown to have ‘significant’ free radical scavenging and/or antioxidant capacity. Researchers also determined other plant polyphenols from medicinal plants had 4 to 5 times the antioxidant capabilities and/or were efficient at much lower dosages in vitro than the standard vitamins E, C, and A antioxidants.
Awkwardly, the concept of free radical scavenging by supplemental antioxidants has been challenged in at least four clinical studies in higher animals and in human clinical trials. [1, 2, 3, 4] It has been demonstrated pretty clearly that the in vitro antioxidant effect did not have the same effect in vivo when measuring free radicals in study subjects. The exception was high dose a-tocopherol (vitamin E) in the prevention of cardiovascular disease . Based on these studies, mainstream medicine has largely deemed antioxidants as worthless or over-hyped products sold as nutritional supplements with little to no benefit. This is largely true if scavenging free radicals is the standard by which antioxidants are judged. Because they don't, or at least not very effectively at all.
Research on antioxidants has gone much beyond scavenging free radicals and this information is simply unknown in the consumer market, and even in some regards, in the natural product manufacturer’s knowledge. Research beginning in the early 2000s began reporting that antioxidants’ main method of action was NOT scavenging free radicals, but they were actually interrupting the complicated chain of events that happen in the intercellular processes the body uses to create a free radical. The terms “chain-breaking antioxidants” and “termination-enhancing antioxidants” were coined and research methods to quantify and measure those effects began to be developed. These compounds supposedly now prevent the formation of free radicals rather than remove or “quench” already formed free radicals. Once again, there were some differences between in vitro measurements/effects and those demonstrated in in vivo in animals and people. Some antioxidants worked in this manner (here's one example), but again, not as well as in vitro results (too many radicals everywhere which too few antioxidant molecules couldn’t reach). There is little consumer knowledge regarding these principles and effects which are complicated and hard to explain to the lay person why one antioxidant works and another doesn’t.
Since a “free radical scavenger mechanism” for nutritional antioxidants cannot be completely substantiated on a kinetic basis in vivo , (whether it scavenges them or reduces the formation of them) what then accounts for the therapeutic effect and benefits of some of these polyphenol antioxidant compounds (like vitamin E and heart disease) used in various diseases and conditions? Studies over the last decade demonstrate that many of the so-called ‘antioxidants’ provide cellular and tissue protection against oxidative damage by inducing the body’s natural antioxidant defenses (ie. superoxide dismutase, glutathione and others chemicals the body produces to fight free radicals more effectively) and through modulating signaling messages between these molecules. Thus, a variety of compounds, including polyphenols, which can act as chemical antioxidants in vitro, have been shown to actually induce enzymatic systems in vivo. So now these antioxidants aren’t scavenging free radicals, they aren’t preventing the formation of them, they are signaling the immune system to create more of it’s own defensive antioxidant chemical to fight them more efficiently.
So now they needed a new method to quantify and qualify these enzyme-catalyzed oxidative processes in vivo and they focused on the oxidation of fat. Outside the body, when fats and oils are oxidized by oxygen they become rancid. The oxidation of fats and oils inside the body is called lipid peroxidation. This process in the body involves fats reacting with oxygen producing hydroperoxyl radicals though a different complicated chain of events. Researchers confirmed lipid peroxidation is inhibited by phenolic antioxidants quenching lipid radicals propagating the chain reactions, and by reduction of lipid hydroperoxides from which radicals are continuously generated.
In some of these in vivo studies researchers were reporting that the antioxidants weren’t scavenging free radicals, they weren’t preventing the formation of free radicals, they were actually protecting cells from the oxidative stress that should have happened when the chain of events occurred, mostly through chemical signaling of the molecules in the chain reaction.
The first report of an antioxidant compound curing a disease through the inhibition of lipid peroxidation occurred in 1992 when vitamin E was used to protect liver cells from chemical damage and reverse cirrhosis. One can also understand vitamin E’s effect on the heart in the previous antioxidant research confirming heart benefits. It wasn’t until much later that scientists discovered why and about the mechanism of action through the signaling effects disrupting the chain of events.
If specific antioxidants (and not all plant chemicals which have in vitro antioxidant actions have this ability) can prevent damage to cells, from specific things known to damage them, that’s a big deal! And it’s something that the marketers and manufacturers of these products aren’t allowed to tell you (but I can!). A good example of this is the antioxidant glutathione, one of the natural compounds produced in the body as a part of the endogenous antioxidant defense system that gets stimulated in the first signaling modification. Research conducted on this compound demonstrated that supplementing with extra glutathione had a cellular protective effect by preventing the damage from oxidative stress that should have been incurred when chemicals were introduced to the brain and the heart. Manufacturers of this supplement knew what this meant but the only thing they could say under FDA regulations was the unhelpful structure/function claims of “supports healthy heart function” and “supports healthy brain function” in their marketing of glutathione supplements. These FDA mandated statements are false and misleading and gave consumers no clue that what it really did was completely protect brain cells and heart cells from damage from substances known to damage them.
So I am going to coin a new term and call these plant compounds and natural chemicals with these abilities and actions “Cellular Protective Antioxidants” and use that in my books, website and blog. Hopefully it will catch on. It will certainly help consumers find the most powerful antioxidants that are providing these actions in living organisms like animals and people. These types of cellular protective antioxidants (most of which come from plant polyphenols) were also those being used to completely protect cells and organs from strong toxic chemotherapy drugs that I blogged about last week in OMG, Cancer & Antioxidants that a normal vitamin antioxidant could never achieve.
Over the last five years, many previously documented antioxidant plant chemicals and plant extracts have been tested to see if they are capable of inhibiting lipid peroxidation in vivo, initially to confirm the compound’s in vitro antioxidant action. When successful, and researchers noticed that these compounds evidenced strong cellular protective effects, protecting cells and organs from oxidative damage that should have occurred, research continued. Some of these plant extracts and most all active plant chemicals found in these extracts that demonstrated this ability went on to other animal studies to determine if this cellular protective effect extended to other harmful chemical agents and/or diseases harming other organs and cells.
In all this research conducted on plant extracts and their chemicals some remarkable cellular protective discoveries have been made. Many of these polyphenol cellular protective compounds have been isolated in rainforest plants, which is why I have been recently exposed to so much of this research as I update the research on the rainforest plants. Just like glutathione is part of the intercellular human defense mechanism against free radicals and oxidative stress, polyphenols are part of a plant’s intercellular defense mechanism against oxidative stress. Stress to plants include intense sunlight burning leaves and fruit, high heat and humidity stressing the plants, healing wounds, and fighting off or repairing the damage caused by numerous species of bacteria, mold, fungi, soil viruses, and insects prevalent in the species-rich Amazon rainforest. Rainforest plants produce an abundance of cellular protective polyphenols chemicals just to survive in the species-rich Amazon.
As I am researching and reading the latest research on the Amazon plants and come across new cellular protective antioxidant plants and chemicals, I am setting these studies aside with the intent to formulate a broad spectrum “cellular protector” formula of rainforest plants that I can use in my protocols. Protocols for cancer, diabetes, aging, and other chronic diseases which all need some type of cellular protection. Maybe I can even get a herbal supplement manufacturer to produce this formula and sell it. Some of these rainforest plants are providing incredible cellular protective actions in the animal studies I’ve read, including for diabetes!
Now. . . What Diabetics Really Need to Know
I have something for diabetics to use in the meantime... and it’s a polyphenol cellular protective antioxidant from a South American tropical plant.
It’s coffee! No, really. I mean it.
First, now that you know what a cellular protective antioxidant is, do some research (if you don’t know) on why oxidative stress and chronic inflammation is probably the underlying cause of Type 2 Diabetes. You’ll also quickly see oxidative stress and inflammation is the main cause in the progression of diabetes and the many complications and co-diseases so prevalent in diabetes. You can start with these:
Why chronic inflammation leads to the progression of diabetes and its complications: Abstract
How addressing oxidative damage can treat diabetes and many diabetic complications: Abstract
One of the best antioxidants for diabetes that addresses both of these issues is found in coffee:
There are two very common polyphenol acids found in many fruits, vegetables and medicinal plants called caffeic acid and quinic acid. When these two chemicals react with one another (or other chemicals, substances, or get activated to defend the plant from something), they create new chemicals which are basically combinations or bonds between these two plant chemicals. These bonds form new unique plant chemicals that are called isomers of these two chemicals. One very well known isomer is called chlorogenic acid which I’ll call CGA for short. This chemical (and it’s parent, caffeic acid), has been proven to have strong cellular protector antioxidant actions in vitro and in vivo, as well as anti-inflammatory, anticancerous, antibacterial and antiviral actions. The richest source of CGA and caffeic acid just happens to be coffee beans. Green un-roasted beans have more CGAs than the roasted/brewed beans do.
It's because of these CGAs that drinking coffee and green tea are now good for you. It wasn't too long ago that doctors told us coffee was to be avoided due to the negative effects of caffeine to the liver. They were wrong (again). Now coffee drinkers have shown to have fewer cancers and live longer. Recent research reports mounting evidence of the reduced risk of developing type 2 diabetes by regular coffee drinkers of 3-4 cups a day.
And, it’s all about the CGAs.
There has been a great deal of research on CGAs being beneficial for diabetics... both to help manage blood sugar levels and improve insulin resistance, as well as to provide the cellular protective actions against the damage and complications to heart, kidneys, nerves, arteries, and liver regularly seen in diabetes. And, CGA’s anti-inflammatory actions help reduce the chronic inflammatory state most diabetics experience which is also implicated in the progression of the disease. This news hasn’t been widely disseminated and many diabetics have never heard of it. For years, there weren’t any CGA health supplement products to buy either - so if you heard about it, you just enjoyed drinking more coffee.
Then BOOM, someone does an animal study that says that CGA promoted weight loss and burned fat in rats and mice and almost overnight, dozens of green coffee bean supplements rich in CGA are available to purchase everywhere. Go figure, huh?
Well, I am adding a green coffee bean supplement to my diabetes protocols, but not for weight loss. In fact, I think the dosages they are promoting for weight loss are too high (based on actual studies) and it would probably achieve weight loss better at lower dosages. For sure, the labeled dosages are too high for diabetics. Animal and human studies (and my own research on some rainforest plants that contain CGA and several other isomers) indicate CGAs work very well at low dosages. It also clearly shows when much higher dosages are used, the beneficial effect is minimized, lost completely, or it produces the opposite effects. You can see that readily in the studies in humans for high blood pressure detailed below.
So here are just some the studies to look at that will show you why I was convinced to put CGA in my diabetes protocols:
Human Studies on diabetes benefits:
Overweight men taking 1 gm CGA reduced glucose and insulin concentrations (0.7 mmol/L and 73 pmol/L, respectively Abstract (Note, I think the effect would have been MUCH better at lower dosages)
CGA modulates glucose uptake and gastrointestinal hormone and insulin secretion in humans: Abstract
Plasma glucose and AUC were significantly lowered (and note lower dosages of CGA were better. Abstract
Animal Studies on diabetes:
CGA protected rats from chemically induced diabetes and in 45 days returned all diabetic markers to normal: Abstract
Diabetic mice given metformin with CGA which inhibited hepatic glucose-6-phosphatase expression and activity, decreased hepatic steatosis (fatty liver), improved lipid profiles and skeletal muscle glucose uptake, which improved fasting glucose levels, glucose tolerance, insulin sensitivity and dyslipidemia: Abstract
Diabetic rats supplemented with CGA for 15 days normalized blood glucose levels, decreased lipid peroxidation levels of main organs and significantly enhanced wound healing: Abstract
In mice with late diabetes CGA lowered the levels of fasting plasma glucose and HbA1c and improved kidney fibrosis: Abstract
CGA improved high fat diet-induced hepatic steatosis (fatty liver) and insulin resistance in mice: Abstract
As I said above, many diabetic complications and progression of other diseases (heart, kidney, nerves, etc) are caused by oxidative stress and/or inflammation. Diabetic rats and mice experience the same diabetic complications and disease progression as humans do and many of these complications have already been reported in animals studies. I believe after reviewing these studies and more, CGA and other isomers might help diabetics avoid many of these complications. For example, diabetic neuropathy is caused by inflammation and oxidative stress and if you look at this study on the causes of neuropathy and then compare it to CGA's immune modulation anti-inflammatory studies below, you can see that CGA modulates almost all of the many enzymes, molecules, transduction signals and other processes related to this diabetic complication. This is showing to be accurate for other complications and co-diseases as shown by the below cellular protective actions documented in the CGA studies below.
Animal Studies on the Cellular Protective actions of CGA:
Protected the eyes of rats from diabetes-related cataract formation: Abstract
Protected the eyes of mice from diabetic retinopathy: Abstract
Protected diabetic rats from necrosis and increased wound healing Abstract
Protected the brains of mice and prevented chemically induced neuropathy: Abstract
Relieved neuropathic pain in diabectic rats: Abstract
Protected diabetic rats from anxiety and memory loss Abstract
Protected diabetic rat kidneys from oxidative stress in diabetic nephropathy: Abstract
Caffeic acid protected rat kidneys from chemical induced damage and inflammation: Abstract
Protected liver from developing steatosis (fatty liver) in rats fed a high cholesterol diet: Abstract
Reduced blot clots significantly (platelet aggregation) in diabetic rats: Abstract
Protected the livers of mice from liver inflammation and fibrosis: Abstract
Protected mice from diabetic sensorineural auditory dysfunction: Abstract
Protected endothelial cells in the heart and reduced hypertension: Abstract
Protected the brains of mice and prevented chemically induced amnesia: Abstract
Protected guinea pig skin against UV-induced oxidative damage: Abstract
Protected GI Tract from a ulcerative chemical in mice: Abstract
Protected livers of rats from damage/failure induced by methamphetamine: Abstract
Protected mice from common species in the gut that are prone to mutate into cancer: Abstract
Confirms in vivo antioxidant action by protecting mice from ischemia-reperfusion injury
(injury/oxidation of tissues by removing blood supply then suddenly returning it) Abstract
Protected the livers of mice from ischemia-reperfusion injury confirming anti-inflammatory and antioxidant actions in vivo: Abstract
Protected the bone marrow of mice from radiation damage: Abstract
Anti-inflammatory Action of CGA:
How CGA reduces inflammation thru immune modulation in vitro: Abstract and Abstract
Confirming in vitro immumomodulatory anti-inflammatory effect in vivo:
Protected the livers of mice from liver inflammation and fibrosis thru immune modulation of inflammation: Abstract
Modulated immune anti-inflammatory response in mice with pleurisy. Abstract
Modulated immune response in rats with induced rheumatoid arthritis: Abstract
Reducing inflammation in mice with colitis: Abstract
Reduced GI tract inflammation in mice: Abstract
Protected rats with spinal cord injuries from inflammation. Abstract
Many more studies on the anti-inflammatory action of CGA can be found here.
Human and Animal Studies on Lowering Blood Pressure:
Healthy subjects were given 400 mg of CGA reported decreased SBP and DBP (-2.41 and -1.53 mmHg, respectively) Abstract
Healthy subjects were given 450 or 900 mg of CGA reported no decrease in SBP and DSP. Abstract
Mild hypertensive subjects given 93 mg CGA reported decreases of SBP and DBP (4.7 and 3.2 mmHg, respectively): Abstract
Mild hypertensive subjects given 140mg CGA reported decreases of SBP and DBP (6.9% and 7.7%.): Abstract
Protected rats from developing high blood pressure by modulating activities of key enzymes: Abstract
Lots more animal and in vitro studies here.
Cholesterol Lowering Actions in Animal Studies:
In obese mice CGA and caffeic acid significantly reduced plasma free fatty acids, triglycerides, and cholesterol, and significantly increased HDL-cholesterol/total cholesterol ratio compared to a high-fat control group. Abstract
In rats fed a high fat diet CGA suppressed increases in serum lipid levels. Abstract
In rat fed a high cholesterol diet CGA (10 mg/kg) significantly reduced total and LDL-cholesterol, increased HDL cholesterol, and improved both the atherogenic index and the cardiac risk factor. Abstract
Anti- Obesity Actions in Animal and Human Studies:
In obese mice, chlorogenic acid and caffeic acid significantly reduced body weight, visceral fat mass, plasma leptin and insulin levels, triglycerides in liver and heart, and cholesterol in adipose tissue and heart compared to the high-fat control group. Only chlorogenic acid significantly lowered triglyceride contents in adipose tissue. Abstract
CGA decreased diet-induced obesity in rats by modulating PPAR and LXR transcription. Abstract
Healthy men and women demonstrated better fat utilization with CGA: Abstract
In vitro AGE-inhibitor actions:
Kim, J., et al. "Chlorogenic acid inhibits the formation of advanced glycation end products and associated protein cross-linking." Arch Pharm Res. 2011 Mar; 34(3): 495-500.
Do an internet search on "advanced glycation end products and diabetes" and learn what they are and how they affect the progression of diabetes and diabetic complications. Start with this study: Abstract
CGA has shown to inhibit the production of AGEs in the test tube. It has not been confirmed in humans or animals. It might be like antioxidants "scavenging free radicals" and just not work the same way in humans as it does in the test tube. We don't know that yet but it would just be icing on cake with all the other benefits of CGA shown above if it in fact did work the same way. The good news is that you can reduce AGEs in your diet, many times, just by changing the way you are cooking your food. This is a good book which will tell you how.
In vitro Anticancerous Actions:
Protected cells from mutation (cancer preventative): Abstract
oral cancers: Abstract
liver cancer Abstract
brain cancer Abstract
estrogen positive breast cancer Abstract
In other in vitro studies CGA has demonstrated antibacterial and antiviral actions. There are lots of other studies reporting in vitro antioxidant, cellular protective, and antidiabetic actions that are just too numerous to list. If you want more, follow this link and start reading.
Rainforest Plants with CGAs
Rainforest plants in the Tropical Plant Database which contain chlorogenic acid as one of it's active plant chemicals include: Yerba mate (green, not toasted, leaves are up to 10% CGA), condurango and artichoke contain chlorogenic and caffeic acids. Cat's claw, macela and embauba contain CGA and other CGA isomers. Many other rainforest plants have other isomers of CGAs, even some unique ones never seen before. Studies like this are being published on various rainforest plants confirming CGA and/or its isomers, and even synergistic actions with other chemicals in the plant providing remarkable cellular protective effects in animals studies (in very low quantities). When researchers are testing a plant extract in animals and notice a particular activity of the extract (anti-diabetic, anti-obesity, anti-inflammatory cellular protective actions and others) then they perform the same tests on some of the extract's chemicals. Many of these demonstrated actions are being attributed to various known CGA isomers (not present in coffee beans) as well as these isomers in conjunction with other plant chemicals present in the plant extract.
Until I have a better source of CGAs with the right dosages and other isomers with cellular protective actions, a green coffee bean supplement is going in my diabetes protocols at dosages of 200mg of CGA daily for individuals that weigh up to 180 pounds. Increase dosages for heavier weight individuals (50 mgs for every 40 pounds more). Do make sure to check your blood sugar levels several times a day when you first starting taking this supplement until you know how your body reacts to it. It has shown in humans and animals to lower glucose levels and your diabetes medication may need adjusting.
There are many green coffee bean supplements to choose from. Do find one that guarantees or standardizes their product to the amount of CGA so you know how much CGA you're getting per capsule/pill . Look for ones that are 400mg capsules with 50% CGA - these will deliver the 200 mgs of CGA. You don't really need the caffeine for the antidiabetic benefits studied above so if you are sensitive to caffeine, buy one of the decaffeinated green coffee supplements available. The caffeine is probably contributing to the weight loss effect, so go with a caffeinated supplement if you want to try and achieve that "side effect." You can find plenty of these supplements to choose from online and on amazon.com
Please come back here and tell us about your results... especially if you are achieving weight loss at these lower dosages. I would love to hear the feedback!