How well is curcumin absorbed, and how bioavailable is it? Unformulated curcumin is absorbed easily but not very bioavailble to the brain.

-Contrary to the myth, curcumin is actually absorbed very well. The problem is 'bioavailabilty' not absorption. It is glucuronidated in the small intestine leading to rapid removal by the kidneys, and the tagged curcumin in less permeable to the brain and has a short half life, while free curcumin is readily permeable to the brain a fatty tissue where it has a long half life. In other words, the more free curcumin, the more rapidly and efficiently it can get into the brain. If it is glucuronidated in the brain, then it is locked there extending half life even more. It rapidly breaks down into vanillin and ferulic acid in plasma, but in the brain it is stable. One strategy is to prevent glucuronidation, but this may interfere with the body's natural ability to rid itself with toxins. Another strategy is to encapsulate and protect it from hydrolysis and to control where in the intestine it is absorbed.

When should I take curcumin? (~2-3 hours before a meal)

It needs to be taken on a virutally empty stomach for optimal absorption (eg. minimum of 3 hours after a meal). You make take it with a small drink (4-6 ounces), best wtih low carbohydrate and high fat and protein (eg coconut milk, whole milk, soy milk). Wait an hour before eating a meal. Most likely taking curcumin before bed is best because you don't have to worry about the next meal.

What form of curcumin should I take and where can I buy it? (Phytosensia Longvida or (Nutrivene Longvida)

There are many forms on the market. If you need it for a peripheral disease arthritis, it any formulation may suffice. One needs to be cautious about claims that absorption is "better than any other formulation". Many of the studies with formulations, to determine blood level, involve collecting plasma treated with an enzymes (glucuronidase and/or sulftase) that break down the tag. This type of data is misleading as brain levels can be high with low plasma levels of free curcumin. We have developed a formulation Longvida. patented by UC Regents, and market to Verdure Sciences. Its development is based on optimizing/maximizing free (untagged) curcumin allowing maximal absorption into the brain and can been purchased from Phytosensia Longvida or Nutrivene Longvida. Each capsule is 500 mg (125 mg of curcumin).

How much curcumin should I take? (unknown somewhere in the range of 4-8 capsules per day based on extrapolation from animal studies)

The precise dose that should be taken has not been determined so one has to extrapolate from animal studies. There is no concern for toxicity since turmeric oleoresin (80% curcumin) is on the FDA's GRAS list. Toxicity may occur at doses 100 fold more than the effective dose. For neuroprotection and neuro anti-inflammatory properties and until trials have been completed, we predict that 4-8 capsules daily should be sufficient. It is very important to start slowly (1-2 capsules daily) then 2-4 capsules 2nd week and so on. It depends on individual variabliity in absorption and formulation. Blood levels of free and metabolized curcumin are not typically measured, but are important to understand efficacious dose. Red blood cell and white blood cell (Buffy Coat) levels of free curcumin parallel brain levels. It has a very short half life in plasma but a very long half life in brain because it is lipophilic (fat-loving). The amount of curcumin one takes depends on whether one needs it peripherally (eg as an antiinflammatory drug for arthritis, where glucuronidated curcumin is efficacious) or in fatty tissues (brain). Because we cannot know without trials the ideal dose we can only extrapolate from animal studies.

What is the cost of Longvida Curcumin? (from $75 to $110 per month)

The cost of Longvida is high, which has to do with the high quality ingredients and a complex manufacturing process. Bottles from Nutrivene normally run for $35.95 for 60 capsules , so taking 4 capsules a day will run about $75 to $80 /per month and 6 capsules a day for $110/ month. For Phytosensia it costs the same , but you need to buy 10 bottles at a time.

What are the immediate effects of Curcumin? Will it help my memory immediately? The effect on memory will likely be gradual. IF there is a a feeling of discomfort then the dose should be adjusted down until symptoms dissipate.

The most obvious initial effect would be a reduction in symptoms of joint pain or other inflammatory conditions. Suddenly taking the full dose in a small percentage of subjects may lead to a feeling similar to drinking coffee or a feeling of agitation. We do not understand the mechanism of this response. One possibility is that since curcumin can clear amyloid from the brain, this may causes a feeling of agitation.so if you if you get this response it is recommended to lower the dose by 2 capsules until the symptoms subside, then go back to maximum dose as soon as symptoms dissipate. Importantly in the naproxen trial for Alzheimer's prevention, naproxen showed prevention of conversion to Alzheimer's, but initially during the first year, subjects memory got worse. It should be determine whether one can avoid a possible deterioration that may occur with 'disease modifying' succesful drugs by lowering dose until symptoms subside.

What is Curcumin? A component of turmeric, a relative of ginger.

Curcumin has been used for thousands of years as a medicinal preparation made from turmeric or as turmeric powder used as a preservative and coloring agent in foods (yellow curry powder). Curcumin was isolated as the major yellow pigment in turmeric, a pure chemical  (diferulomethane).  Curcumin’s structure is similar to other plant pigments called polyphenolics (chemicals containing muliple “phenol” groups) which often have potent anti-oxidant and anti-inflammatory properties and associated health benefits. Many similar plant pigments are known as potent antioxidants, for example, the pigments extracted from grapes in red wine ( resveratrol), or in green tea (catechins) or in fruit juices (blueberries, strawberries, pomegranates etc) typically contain polyphenolic antioxidants and have been studied for their possible medicinal or preventive value.

Why should I consider taking DHA with curcumin?

Animal studies suggest that curcumin and fish oil synergize.

What form of DHA and how much?

Again clinical studies are necessary. Data suggest that subjects with E4 do not respond to DHA which may be due to oxidation. It is possible that Curcumin or other antioxidants may enable ApoE4 to respond to DHA. A combination of pure DHA with fish oil is recommended.

600-900 mg of DHA is recommended. You can start with a higher loading dose than drop down. Higher doses were used in the trial but there is saturation at 900 mg/day. One gram of fish oil has about 200 mg of DHA, so one could take 3-5 capules of fish oil. Or 2 capsules of Fish oil and 1 capsule of pure "algae" DHA. Fish oil impacts platelets, so watch for bruising and if on plavix, warfarin or related blood thinners, make sure to check clotting and adjust blood thinner appropriately.

• Of the many polyphenolics, curcumin is special for the following reasons:

• Curcumin is the Asian version of aspirin.  Our wonder drug aspirin was originally purifed from willow bark extracts that were used in European and American Indian traditional medicines to control inflammation. Eventually aspirin was synthesized by German chemists and developed by Bayer as one of the most successful drugs in the Western medicine cabinet. Today aspirin is used not only in pain remedies and other analgesic applications, but to control minor fever and inflammation and, at low doses, to prevent heart attack and stroke.  Curcumin has been used in traditional Indian (Ayruvedic) and Chinese medicine for thousands of years largely because of its proven efficacy in treating conditions with inflammation. They also used it in foods as an effective food preservative, just as we use synthetic additives like BHA. These ancient civilizations have vast trial and error experience with many different herbal remedies and food preparations and they selected curcumin as a food additive and major tool for medicinal use based on efficacy- not superstition.

• Curcumin has been developed by the US National Cancer Institute (NCI) and academic investigators around the world as a potent anti-carcinogen. Because of low toxicity and great efficacy in multiple in vitro and in vivo cancer models, curcumin was selected for further development, put through extensive toxicology testing and has successively made it through the first stages (Phase I) of clinical testing abroad and is currently in clinical trials at several sites in the U.S. All of this work by many labs has provided the basis to quickly and safely explore curcumin’s potential for Alzheimer’s and other neurological diseases.

• Curcumin has shown efficacy in many other pre-clinical culture and animal models for diseases related to aging and chronic treatment with related “curcuminoids” have even been able to increase the lifespan of mice.

• Curcumin and Alzheimer’s Disease.  Our group has tested curcumin in several models for Alzheimer’s and found that it not only reduces oxidative damage and inflammation (as expected), but also reduces amyloid accumulation and synaptic marker loss and promotes amyloid phagocytosis and clearance. Curcumin worked to prevent synaptic marker and cognitive deficits caused by amyloid peptide infusion and abeta oligomer toxicity in vitro. Our work on curcumin and AD is discussed in detail in our publications. and for information on enrolling in a curcumin trial see trials link . For news releases see News link.

1. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA. J Biol Chem. 2013 Feb 8;288(6):4056-65.
2. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM. Alzheimers Res Ther. 2012 Oct 29;4(5):43.
3. Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease. Hickey MA, Zhu C, Medvedeva V, Lerner RP, Patassini S, Franich NR, Maiti P, Frautschy SA, Zeitlin S, Levine MS, Chesselet MF. Mol Neurodegener. 2012 Apr 4;7:12. doi: 10.1186/1750-1326-7-12.
4. Why pleiotropic interventions are needed for Alzheimer's disease. Frautschy SA, Cole GM. Mol Neurobiol. 2010 Jun;41(2-3):392-409. doi: 10.1007/s12035-010-8137-1.
5. . Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM. J Neurosci. 2009
6. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208. doi: 10.1124/jpet.108.137455.
7. Heath DD, Pruitt MA, Brenner DE, Begum AN, Frautschy SA, Rock CL. Tetrahydrocurcumin in plasma and urine: Quantitation by high performance liquid chromatography.J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 29; [Epub ahead of print]
   PMID: 16061427 [PubMed - as supplied by publisher]
   
8. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer's disease.Curr Alzheimer Res. 2005 Apr;2(2):131-6.PMID: 15974909 [PubMed - in process]
   
9. Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA. NSAID and Antioxidant Prevention of Alzheimer's Disease: Lessons from In Vitro and Animal Models.Ann N Y Acad Sci. 2004 Dec;1035:68-84.PMID: 15681801 [PubMed - in process]
   
10. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.
    J Biol Chem. 2005 Feb 18;280(7):5892-901. Epub 2004 Dec 7.PMID: 15590663 [PubMed - indexed for MEDLINE]
    
11. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005. PMID: 11755008 [PubMed - indexed for MEDLINE]
    
12. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. Related Articles The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.J Neurosci. 2001 Nov 1;21(21):8370-7.PMID: 11606625 [PubMed - indexed for MEDLINE]