Frequently Asked Questions

  • Questions:
  • Questions on Curcumin


  • What is curcumin, and where does it come from?

Turmeric is about 4% curcumin so it is hard to get a lot from it. . Curcumin can be purchased as an extract of turmeric over the internet or in health food stores. Safety and toxicity testing on curcumin are extensive and very reassuring.

  • How does curcumin work as an AD treatment?

Curcumin has potent antioxidant and anti-inflammatory activies in animal models of other neurodegenerative diseases, including stroke, traumatic brain injury, multiple sclerosis, as well as atherosclerosis and several cancer models.Curcumin is one of the treatments that seems to work in AD animal models.   Curcumin could act at several levels in the AD pathogenesis, but we have not identified which action of curcumin is the most important, or whether the separate actions synergize with one another. Curcumin is a potent antioxidant and antiinflammatory, and it has amyloid aggregation inhibiting activity. Through these activities, it induces Phase II enzymes.  The benefits have been replicated in both transgenic mouse models and rat infusion models, suggesting the need for testing clinically.

  • Does curcumin do anything else besides effects on inflammation and oxidation

One known cause of AD is increased amyloid 42 (AB42) production and its subsequent aggregation. Curcumin has a chemical structure similar to chemicals (congo red) that bind AB aggregates, and we have shown that curcumin inhibits AB aggregation, probably by inhibiting protein beta sheet formation (Yang et al.). Curcumin is being tested in other neurodegenerative disease models, particularly those involving protein accumulations (like the amyloid in AD).  Marie-Francoise Chesselet at UCLA is working on curcumin and Huntingtion’s disease in animal models. Curcumin also blocks prion aggregate formation in vitro very well at about 200nm levels (B. Caughey)  and and it probably blocks some CAG repeat proteins since congo red can.

Its is an amyloid binding compound because of the spacing between the rings and can deaggregate  toxic fibrils and oligomers of amyloid. The deaggregating effects  have been replicated by other groups. Also it stimulates inflammatory clearance of amyloid similar to the vaccine, and a group in Japan has reported its effect on reducing tau aggregation associated with neurofibrillary tangle formation. Finally the bridge between the two phenolics helps bind metals like iron, which may render some of its beneficial effects.

  • What dose of curcumin should I take, how should I take it, are there side effects, are there drug interactions?

We have to recommmend that people wait until our UCLA trial or other trials produces positive results for curcumin in ameliorating cognitive deficits like those in AD in order to have anadequate understanding of dosing, but for some people, time is of the essence.

For any drug, dose is the critical issue with both safety and efficacy. We have a small pilot clinical trial at UCLA which is testing two fairly high doses of 2,000 and 4,000 mgs of curcumin manufactured as an extract by Sabinsa ( good on line website). Long term trials have not shown side effects at ~1200 mg for 3 years while short term (3 months) trials in cancer patients report no problems up to 8 gms a day, but other studies suggest some patients get diarrhea at 3 or 4 gms. The phase I trials in cancer patients showed 2/15 patients had diarhhea at 3.6 gms at the end of the 3 month trial. (Search R. Sharma (Leicester England) for the 2004 Clinical Cancer Res. paper.). The most common side effects, although not that common, are GI tract issues (signs of bleeding) or biliary obstruction.

It is possible that only 500mg would be effective. I would suggest to start on around 500-1,000 mg a day and gradually increasing the dose, maybe going up to 2,000 mg if there are no side effect problems, but not higher. I have never heard of a problem with people taking <2000 mg, but it could happen. At 2 gms a day, curcumin appears very safe. At 4 gms a day, it is clearly anti-inflammatory in patients, but there could be safety issues.

One reason the doses are so high is poor absorption. Curcumin is poorly absorbed and should be taken with a fatty meal. We believe that curcumin synergizes with omega-3 fatty acids in AD and probably other neurodegenerative conditions and would suggest taking it with fish oil or algal DHA, based on our animal data (see the section on DHA/omega-3 fatty acids). Whether as an extract (pure curcumin) or turmeric itself, fats probably help absorption and reduce the likelihood of diarrhea if very high doses are taken. Alternatively, absorption may also be increased with 2 hr fasting. Saftey and toxicity will be evaluated when we are able to get higher doses of curcumin delivered to the brain.

            We are currently seeking grant support to address the issue of curcumin bioavailability which is a problem that we think we can solve; at least we have some reasonable methods to test (fasting, fats, other formulations).  It would be very useful to test lower doses in clinical trials, but that will take siginificantly more grant funding.

We am unaware of a drug interaction problems, but it is always possible. There could be an interaction with NSAIDs since curcumin is anti-inflammatory. Conceivably, there could be interactions with blood thinners.

  • Can I participate in a clinical trial for curcumin?

Participating in a clinical trial is the safest way to take curcumin for treatment of AD-related symptoms, because of the great safety of being under direct medical supervision (looking for signs of side effects) as well as objectively determining whether there it is working for you as an individual, since, as in all clinical trials, different people respond differently.   The clinical trial coordinator at UCLA is…

            Outside of UCLA, there are no other curcumin trial sites for cognitive treatment.  Consult your doctor I fyou plan to take curcumin a nd discuss the possible side effects and how to monitor for them.

For other treatments, the AlzForum website lists most AD clinical trials.  Participating in these trials is of great help to the field of AD treatments. There are many trials with centers throught the USA, Europe, and elsewhere in the world.


  • Questions


  • Do the cholinesterase inhibitors work?

Current cholinesterase inhibitor therapies are not a very potent treatment. The cholinesterase inhibitors have significant effects between groups and in some patients they have an emotionally significant impact, but people continue to decline in the AD disease progression

  • Are there alternatives to the cholinestease inhibitors as treatments that slow, stop, or reverse AD symptoms?

There are many new therapies being tried for Alzheimer's based on the beta-amyloid cascade hypothesis and successful results in transgenic mouse models.

There is great interest in a treatment developed by Elan Pharmaceutical, South San Francisco and Dublin, Ireland using passive immunization with anti-AB antibodies instead of active immunization as with their "vaccine" clinical trial. Animal models with human AD disease genes have been used to show that the "vaccine" treatments (active and passive) have therepeutic potential.

Eli Lilly has a gamma secretase inhibitor trial aimed at reducing AB production. 

The AlzForum website lists most clinical trials.  Participating in these trials is of great help to the field of AD treatments.  There are many trials with centers throughout the USA, Europe, and elsewhere in the world.

Other possible therapies include physical exercise and increasing cerebral spinal fluid flow (see these presented in the FAQ section).

  • Questions


  • What makes fish oil good”

Fish oil is rich in the essential fatty acids called omega-3 fatty acids, also known as DHA (docosahexaenoic acid).  It is well known that societies that eat a lot of fish have fewer health problems, particularly cadiovascular and maybe cognitive problems.  Since they are “essential”, meaning they cannot be synthesized by our body and must be obtained in the diet, they must be constantly replaced as they wear out, primarily by being oxidized.  This can lead to cardiovasular problems including the accumulation of fats in the arteries.  If your intake of omega-3 is low, then the oxidized omega-3 in your body remains and causes problems in the efficient functioning of cells, particularly their membranes where fatty acids reside.  Neuron cells are particularly reliant on efficient functioning of their cellular membranes.  By increasing your dietary intake of omega-3 fatty acids, you replace the oxidized fats with unoxidized form, essentially cleaning your body of the worn out fats, which leads to improved cell functions and fat profiles in your blood

  • Is fish oil recommended to improve health? How much should I take?

American Heart Association recommendations:

The american heart association recommends 2 or 3 fish oil capsules (1gm each) a day, based on clinical trial and safety data. (One 1000 mg Capsules normally contain about 180 mg of DHA and 220 mg EPA. ) For replenishment of a depleted adult brain, it may be a disadvantage to have more EPA than DHA, because EPA can compette for incorporation of DHA into membranes. It may be wise to supplement fish oil capsules with purified DHA (eg neuromins200 from algae sold by Martek see also section on lifestyle and diet.

  • Is fish oil/DHA useful for cognitive or behavioral problems?

Fish oil has been studies for behavioral disorders like depression and seems to show positive benefits. 

  • How much fish oil should I take to improve cognition problems like those in AD?

Unfortunately, current recommendations about dose and efficacy are just "guestimates" since there is no trial data omega 3 fatty acids. DHA will go into large multicenter trials for cognitive impaiment (MCI and/or AD), but doses for those trials has not been determined yet.

  • Should I be worried about mercury contamination in fish

In general, levels of mercury in fish oil supplements have been shown to be very low.  Listed here are the critical papers, and articles for the public, and web sites concerning  this issue.  Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med. 2003 Dec;127(12):1603-5. PMID: 14632570 The levels of mercury in the 5 different brands of fish oil ranged from nondetectable (<6 microg/L) to negligible (10-12 microg/L). The mercury content of fish oil was similar to the basal concentration normally found in human blood. CONCLUSIONS: Fish are rich in omega-3 fatty acids, and their consumption is recommended to decrease the risk of coronary artery disease. However, fish such as swordfish and shark are also a source of exposure to the heavy metal toxin, mercury. The fish oil brands examined in this manuscript have negligible amounts of mercury and may provide a safer alternative to fish consumption. Harv Womens Health Watch. 2004 Sep;12(1):8. By the way, doctor. The stories about mercury and other toxins in fish have me worried that my fish oil supplements may be contaminated. Have there been any studies of these toxins in fish oil capsules? Robb-Nicholson C. PMID: 15381474   Mayo Clin Womens Healthsource. 2004 Feb;8(2):8. I read about fish oil supplements in your September issue. Should I be concerned about mercury levels in these products? [No authors listed] PMID: 14722493  US Environmental Protection Agency’s National Listing of Fish and Wildlife Advisories US Food and Drug Administration’s list of mercury content of selected fish US Geological survey: Mercury in the Environment

  • What is the current reference dose for mercury?

A reference dose (RfD) is the estimated daily dose of a substance that can be consumed safely over a lifetime, even for sensitive populations.

In 1996, EPA established the current RfD for mercury of 0.1 micrograms per kilogram of body weight per day. However, the Food and Drug Administration (FDA) and the Agency for Toxic Substances and Disease Registry (ATSDR) have recommended regulatory levels that are significantly less stringent than EPA's reference dose.

FDA has established an acceptable daily intake for mercury of 0.4 micrograms per kilogram of body weight per day. ATSDR has stated that "daily intake of methylmercury at a level of 0.3 micrograms per kilogram [of] body weight per day for extended periods up to a lifetime presents no risk of adverse health outcomes in even the most sensitive human populations (pregnant women, developing fetuses, and young children)."7 In 2003, the World Health Organization ("WHO") revised its recommendation for safe intake levels for mercury in food to 1.6 micrograms per kilogram of body weight per week. In fact, the reference dose for mercury adopted by WHO is more than two times greater, and ATSDR's is three times greater, than EPA's reference dose. EPA's reference dose is the lowest due to the inclusion of an extremely conservative safety factor.

Sierra Club Warnings


According to a February 3 report by the EPA's Inspector General Nikki Tinsley, EPA political appointees set "modest" new mercury pollution limits that just so happened to coincide with those in President Bush's "Clear Skies" proposal. They then told EPA scientists to work backwards to justify those limits. She also found that the EPA did not adequately evaluate the environmental health effects of the proposed rule on children. "Rather than basing its decision on good science, the administration stacked the deck to give its industry friends what they wanted," says Nat Mund, a Sierra Club clean-air expert. One in six American women has mercury levels in her blood high enough to put her baby at risk from mercury poisoning.

  • Are there other toxins in fish oil?

Melanson SF, Lewandrowski EL, Flood JG, Lewandrowski KB. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med. 2005 Jan;129(1):74-7. PMID: 15628911 . The levels of polychlorinated biphenyls and organochlorines were all below the detectable limit. CONCLUSIONS: Fish oil supplements are more healthful than the consumption of fish high in organochlorines. Fish oils provide the benefits of omega-3 fatty acids without the risk of toxicity.

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