Curcumin, Thioflavin T, and Rosmarinic Acid Fight Damaging Amyloid Beta Proteins of Alzheimer’s Disease

Researchers in the past several years have identified compounds that have strong effects against factors suspected to be responsible for much of the damage to the brain seen in Alzheimer’s Disease patients. Two of these compounds, curcumin and rosmarinic acid, are found in widely used spices and herbs such as turmeric (a yellow Indian curry spice) and rosemary, sage, thyme, and mint variants such as lemon balm (Melissa officinalis) and thus herbs and spices may represent safe and relatively inexpensive sources for these compounds. A third compound, Thioflavin T, is a dye used in research and diagnostic settings.

India and Southeast Asian are areas where turmeric and curcumin are widely consumed. It has been noted that their age-adjusted rate of Alzheimer’s Disease seems notably lower (only around 20% to 25% of Western nations by some studies) than that of populations that do not consume so much turmeric and curcumin. There’s an interesting map of Alzheimer’s and dementia death rates by country that further illustrates very drastic regional differences, but unfortunately it does not appear to be age-adjusted.

Medical Research Dye Binds to Amyloid Beta Proteins

Of the three compounds, the yellowish medical dye Thioflavin T appears it may have the highest activity at aiding the body in eliminating the amyloid beta proteins believed to be a primary culprit in Alzeimer’s Disease. The dye is widely used in medical research for Alzheimer’s, but the safety and efficacy in live humans has not yet been established. How they work is not totally clear, but it appears it may involve multiple mechanisms. It is thought that the dye destabilizes amyloid beta proteins to make them fall apart, prevents clumping and abnormal folding of proteins, and “tags” amyloid beta thereby making it easier for the immune system to identify and attack these toxic substances.

The researchers at the Buck Institute for Research on Aging who studied Thioflavin T examined the effects of 10 compounds and noted that in addition to Thioflavin T, curcumin also looks particularly promising. Like Thioflavin T, curcumin was noted for its ability to improve the lifespans two groups of nematode worms (species Caenorhabditis elegans), one that was normal and another that was bred to be used as a model for Alzheimer’s Disease. Both compounds appear to “slow aging” by reducing the buildup of damaged proteins in the worms. Following these exciting findings, the researchers are moving on to studies in mice.

The study found that Thioflavin T could boost nematode lifespan by about 78%, adding about two weeks life to the worms that normally live about two to three weeks. The researchers have filed a patent on using Thioflavin T to increase lifespan.

Curcumin Counteracts Amyloid Beta Proteins

Curcumin is among the main active ingredients in the yellowish Indian spice turmeric that has been used for more than 2000 years in Indian and Chinese cuisine and medicine. The researchers who identified the mechanisms for action for Thioflavin T think that curcumin may also operate a lot like Thioflavin T. Curcumin and a compound rifamicin added about 45% to lifespan to the nematode worms in the study, not as much as the 78% for Thioflavin T but still very significant.

Both Thioflavin T and curcumin appear to inhibit buildup of amyloid beta proteins and to help eradicate those already formed. Thus it is possible that therapies could be developed both for preventative uses as well as for treating patients who already suffer from Alzheimer’s. One potential challenge is that there is little evidence as to whether either compound crosses the blood-brain barrier effectively.

Presently it is much easier for the average consumer to obtain curcumin and turmeric products than Thioflavin T. That’s probably a good thing because researchers found that very high dosages of Thioflavin T can kill nematode worms via toxicity. Thus there is reason to believe there may be a higher risk of toxic side effects in humans from the dye than there is from curcumin.

Curcumin Researched for Role Against TNF-a Inflammation

Epidemiological studies have suggested that a lower rate of Alzheimer’s in Indian populations that eat a lot of the spice might have something to do with the anti-inflammatory benefits of turmeric. Curcumin in the past decade or so has become widely known for its ability to inhibit activity of the inflammatory cytokine Tumor Necrosis Factor alpha (TNF-a) and is being researched for use in many diseases involving inflammatory conditions including Alzheimer’s, arthritis, atherosclerosis, and asthma. It’s also being studied for use in fighting sepsis and radiation induced tissue damage, both of which feature great harm caused by inflammation.

Curcumin is one of the components of turmeric, but there are others such a turmeric oils that are believed to have effect against the inflammatory PGE2 (prostaglandin E2), unlike curcumin itself. Curcumin has also been found to inhibit COX-2 and NF-kB (Nuclear Factor kappa B) which are additional inflammatory factors. NF-kB is known to promote the generation of TNF-a and IL-1 (Interleukin 1) and IL-6 (Interleukin 6) inflammatory factors that are often elevated in Alzheimer’s patients, so it’s possible that curcumin could be highly beneficial at fighting the illness from many angles involving inflammatory processes.

TNF-a Inhibitor Enbrel Found to Benefit Alzheimer’s Patients

In 2008, researchers announced that the drug Enbrel (generic name etanercept) when injected into cerebrospinal fluid (known as perispinal administration) reaches the brains of Alzheimer’s patients and causes a major improvement in symptoms starting in just minutes after treatment. It is believed the effect is largely due to Enbrel’s inhibition of TNF-a. Reports are that cognitive ability, mood, and daily activities all improve markedly in patients getting perispinal Enbrel injections. As exciting as this news is, the therapy is expensive and invasive and the medicine itself is also expensive. Interestingly, Enbrel was originally developed for treating arthritis via its TNF-a inhibition in which it mops up excess TNF-a in the body before it can produce inflammatory damage. Enbrel for arthritis is administered via subcutaneous injection.


Rosmarinic Acid Fights Oxidative Damage Related to Amyloid Beta Proteins

Rosmarinic acid, found in many common herbs including rosemary, sage, and thyme, works as an antioxidant that is particularly potent at fighting peroxynitrites associated with amyloid beta damage. Thus herbal sources of rosmarinic acid could make a good addition to any kind of therapy using curcumin for Alzheimer’s, helping to mop up free radicals triggered by the toxic proteins. Curcumin itself is also reputed to have antioxidant effects.

Many supplements have antioxidant and/or anti-inflammatory properties are helpful for a wide variety of health conditions. However, each individual compound tends to be capable of acting on only one or at most a few forms of free radicals or inflammatory factors. Thus it is often helpful to mix and match compounds and supplements to achieve a broad action against many kinds of oxidative and inflammatory agents.

For instance, green tea extracts containing catechins and EGCG have also been mentioned as possibly beneficial to ameliorating oxidative damage from conditions such as Alzheimer’s. There’s also research suggesting that EGCG itself may help prevent formation of amyloid beta plaques.

Poor Bioavailability of Common Turmeric and Curcumin Supplements

One of the big challenges to effectively using turmeric as a nutritional supplement is the poor bioavailability of curcumin in its raw form. It’s possible to increase absorption somewhat by eating it with some oily foods, but studies on curcumin absorption in humans indicate that the vast majority of it is excreted via digestive tract waste. Fortunately, there at at least four major types of enhanced bioavailability curcumin supplements introduced during the last several years. For more information, please read High Bioavailability Curcumin Supplements from Indena, Dolcas Biotech, and Verdure Sciences.

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Further Reading

Life Extension’s Alzheimer’s Disease Protocol

Can Curcumin Prevent Alzheimer’s Disease?

Alternative Approach : Spicy Curcumin Might Help You Avoid Alzheimer’s

How Curcumin Protects Against Cancer

Curcumin may offer protection against diabetes

Buck Institute finds secrets of longevity – in roundworms

Extending Worms’ Lives, and Maybe Ours

Nature study shows common lab dye is a wonder drug — for worms

Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan

Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation

Dyeing Worms for an Extra-Long, Healthy Lifespan?

Linus Pauling Institute: Curcumin

Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer’s Disease

Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro

The development of preventives and therapeutics for Alzheimer’s disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta

Inhibition of tumor necrosis factor by curcumin, a phytochemical

A Curcuminoid and Sesquiterpenes as Inhibitors of Macrophage TNF-α Release from Curcuma zedoaria

Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis

The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

The effect of turmeric extracts on inflammatory mediator production

New Hybrid Drug, Derived from Common Spice, May Protect, Rebuild Brain Cells After Stroke

Turmeric and Alzheimer ’s disease

The “Real Curcumin” for Treating Alzheimer’s, Parkinson’s and Other Brain Diseases

Reversal Of Alzheimer’s Symptoms Within Minutes In Human Study

Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration

The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-beta peptide-induced neurotoxicity

A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25–35

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial

Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein Cleavage and Reduces Cerebral Amyloidosis in Alzheimer Transgenic Mice


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Comments

Curcumin, Thioflavin T, and Rosmarinic Acid Fight Damaging Amyloid Beta Proteins of Alzheimer’s Disease — 3 Comments

  1. I love Indian food, especially curries. How much curcumin is too much? Is there any sign of it being toxic?

    • In theory curcumin could be toxic if consumed in truly massive dosages. But you’d probably get tired of eating it before that happened.

      I found mention of a University of Michigan curcumin dosage study in humans in 2006 using a 95% curcumin extract from Sabinsa Corporation (not with piperine). The researchers examined single dosages up to 12 grams (12,000 mg) with no or minimal toxicity observed. They found no measureable curcumin in the blood of the human volunteers until they reached 10,000 mg dosages. As an indicator of the peak levels of curcumin from these high dosages, one of the study subjects had a measured level of curcumin of 57.6 ng/mL about 2 hours after the 12,000 mg dose.

      The authors pointed out that this small absorption into the blood could mean curcumin could be really helpful for dealing with colorectal cancer as a long-term chemopreventive agent as the compound would mostly stay concentrated in the digestive tract. In the article above, I speculated for similar reasons (that most of the orally ingested curcumin is excreted via the digestive tract) that typical low bioavailability turmeric or curcumin may be helpful for preventing Helicobacter pylori infections by making the digestive system less hospitable to the infectious bacteria.

      A 2001 study in Taiwan of curcumin as a chemopreventive agent concluded that oral consumption of up to 8000 mg per day per curcumin for 3 months showed no significant evidence of toxicity.

      A recent rat study tested a highly bioavailable curcumin formulation and found that the LD(50) (the single dose that kills half the rats) was greater than 2000 mg per kilogram body weight. It also noted that the no adverse effects level in the rats was 720 mg per kilogram body weight per day. Rat studies can’t be translated directly to humans, but they are at least a good hint that the dosages of even high bioavailability curcumin would have to be many grams per day before it is likely to affect a healthy human adversely.

      One seemingly strange observation that I did find was that curcumin might be a contraceptive at high concentrations by impairing sperm motility. See Can curcumin provide an ideal contraceptive? for more information. It’s my guess that such concentrations probably could not be reached easily via normal diet or supplementation. As evidence of that, I’d cite the rapidly growing population of India where turmeric and curcumin are widely consumed and how it has also been noted that their rate of Alzheimer’s Disease seems notably lower than that of populations that do not consume so much turmeric and curcumin.

  2. If one reads through these articles carefully, he or she will find the answer to preventing and treating Alzheimer’s disease. Phenolic compounds (contained in various vegetables, fruits, spices, and essential oils) and polyunsaturated fats (such as fish oil) inhibit the formation of peroxynitrites–the main compound responsible for Alzheimer’s disease. They do so by inhibiting the activation of phospholipase C gamma as well as the later TNF-alpha induction of peroxynitrites. Morevover, phenolic compounds scavenge peroxynitrites (convert them into a less dangerous), inhibit and partially reverse the peroxynitrite nitration of tau proteins (thus improving neurotransmissions) and partially reverse the peroxynitrite oxidation of glucose transport systems (increasing energy and awareness). They increase short-term memory by increasing acetylcholine levels as they partially reverse the oxidation of choline transport systems, muscarinic recpetors (involved in the uptake of choline) and the enzyme choline acetyltransferase. Phenolic compounds also paritally reverse the oxidation of receptors involved in smell (olfactory), sleep and mood (serotonin), alertness (dopamaine), and adrenergic (behavior). To date every phenolic peroxynitrite scavenger–grape seed extract, rosmarinic acid, cinnamon extract, eugenol in Cinnamomum zeylanicum essential oil, and thymol and carvacrol in Zataria multiflora Boiss.) have corrected cognitive deficits in animal models of Alzheimer’s disease. In addition, small-scale clinical trials using aromatherapy or tinctures of essential oils have led to improvements in cognitive function in patients with dementia, including those with Alzheimer’s disease (see the clinical trial conducted by Jimbo and his colleagues, for instance). Several individual and institutional case studies using aromatherapy to treat Alzheimer’s disease have also produced successful results (the largest was the Texas State Research on Aromatherapy). Essential oils high in eugenol, thymol, and carvacrol include cinnamon leaf, sage, rosemary, clove, lemon balm, oregano, and thyme. These compounds can be directly inhaled into the hippocampus–the part of the brain most damaged by Alzheimer’s disease–through aromatherapy. Indeed, the ability to prevent and treat this horrible disease is at hand.

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