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As the advancements in the formulation of curcumin too provide much higher absorbability by the body, along with passing it through the blood-brain barrier, we continue to hear more about the benefits of this great supplement. For years, many studies have shown that curcumin has the ability to assist the body with many health issues. Unfortunately this was only done in the lab inasmuch as when taking raw curcumin, most of it simply passes through the body without entering into the blood stream.
Unfortunately, many people are still hoping for benefits of curcumin by continuing to take older formulations that are not nearly as effective and may not be resulting in the health benefits they are looking for. Many people take turmeric based on the fact that it is the plant that contains curcumin. There are two issues here, one is that there is a very small amount of curcumin in the turmeric, and two, very little of the small amount of curcumin is actually absorbed by the body. Curcumin is not water-soluble making it very difficult for the body to absorb it.
Others realize that it would be more beneficial to take a product that contains raw curcumin that has been extracted from the turmeric root. As stated above this does not result in any significant benefit. There has been a improvement in absorption of curcumin using a bio-perrine (pepper) process, but still it results in a very small amount being absorbed by the body.
A significant advancement was made in the development of a curcumin product referred to as "BCM-95". It contains a significant amount of raw curcumin, along with natural oils from the turmeric root. This provides a much higher amount of absorbability into the body. This formulation has been most beneficial to people with inflamation issues as well as providing relief for some cancer issues, especially in conjunction with chemortherapy treatments. Unfortunately, BCM-95 curcumin does not demonstrate the ability to penetrate the blood-brain barrier.
A significant breakthrough in improving the bioavailability of curcumin was made in the development of "Solid Lipid Curcumin Particle" technology by the elite neuroscientists at UCLA. SLCP™ Technology is an an absorption promoting technology that protects free curcumin from initial hydrolysis, allowing the uptake of free curcumin and delivering bioefficcious levels into the bloodstream, target tissues, and the brain. The end product preserves the natural spectrum curcumin from the harsh environment of the stomach, dissolves it at the point of absorption in the GI tract, and delivers the free form (also called intact or native) into the blood stream and target tissues. The end result is achieving a very high amount of absorbability of free curcumin by the body and effectively delivering it where it is most needed by the body.
Powered by patented (US Patent 9192644, EP Patent 1993365; additional patents pending) SLCP™ Technology, Longvida® Optimized Curcumin is a breakthrough formula of the natural antioxidant curcumin, from the turmeric root. It is optimized to deliver free curcumin into target tissues through the critical bioavailability requirements of permeability, solubility, and stability. Developed in collaboration with elite neuroscientists at UCLA, Longvida® carries a strong safety profile and is self-GRAS.
While the higher absorption of curcumin has the potential to improve many of our bodies ailments, one of the most significant might be in the treatment of dementia. The United States has an Alzheimer’s/dementia death rate which is the 2nd worst in the world (2nd only to Finland). Finland is 53.77 per 100,000 (age standardized), the US isn’t much better at 45.58. Now compare those numbers to 0.46 per 100,000 for India18.
Does India’s high dietary usage of turmeric have anything to do with that? If so – as some theorize – then it’s being accomplished without any special patented or proprietary ingredients for increasing absorption. However, they consume a very large amount of turmeric throughout their lifetime.
A study at UCLA demonstrated a significant improvement in dementia. You can read the report by clicking on the link at the top of the page.
What is curcumin?
Curcumin, is an anti-inflammatory molecule in the turmeric root, a relative of ginger. Turmeric has been used for thousands of years as a medicinal preparation and a preservative and coloring agent in foods. Curcumin was isolated as the major yellow pigment in turmeric; chemically diferulomethane, and has a polyphenolic molecular structure similar to other plant pigments (eg. extracted from grapes in wine (resveratrol), or in green tea (catechins) or in certain fruit juices (blueberries, strawberries, pomegranates etc.) This polyphenols share in common anti-oxidant and anti-inflammatory properties with associated health benefits
Can eating turmeric-based curries, increase curcumin levels in the blood?
India has a low incidence and prevalance of Alzheimer's, which may be related to genetics or a particular intake of specific foods. Some people attribute the low incidence of Alzheimer's to a high intake of turmeric in Asia. As turmeric contains an average of 5-10% curcumin, the daily intake of curcumin is approximated in India is thought be about 125 mg. Importantly incooking curries, curcumin is often dissolved and extracted into fat, eg. ghee, which may increase its bioavailability. Animal studies have demonstrated that the way it is administered affects its distribution in the body. Unformulated curcumin, such as purified and dried curcumin in a capsule, is absorbed easily but the liver and GI tract tag it in a way that make it not very bioavailable to the brain. There is a lot of confusion about curcumin bioavailability versus absorption. Curcumin is absorbed, but not necessarily bioavailable. Further GI and liver glucuronidation or sulfation "tagged curcumin" which interfere with bioavailability it some tissues also leadds to its rapid removal by the kidneys. Unliked tagged curcumin, free curcumin readily crossed the blood brain barrier and is relatively stable.
To increase free curcumin and its half life, one company Sabinsa has used the strategy to reduce curcumin's clearance by inhibiting glucuronidation using piperine (Sabinsa C3 complex). Glucuronidation is a method to to rid the body of toxins and remove metabolized drugs. Therefore one should determine blood levels of currently used medications after taking this formulation for several days.
Other proposed strategies are to increase its solubility (Meriva), or to encapsulate and protect it from hydrolysis and to control where in the intestine it is absorbed (Longvida).
In summary curcumin is easily absorbed but not necessarily very bioavailable to the brain (such as dissolved in cooking oils or formulated). It is stable in fatty tissues such as the brain, but not in blood.
If I decide to take curcumin in capsule form, should I choose pure curcumin or a formulation?
There are many formulations on the market. If you decide to take curcumin for a disease peripheral to the brain such as arthritis, any formulation may suffice. There are two essential criteria to consider, first, is there evidence that the formulation will lead to adequate curcumin levels in the target tissue?, and second is the formulation manufactured by a company with Good Manufacturing Practice (GMP). Since curcumin is a metal chelator it can chelate toxic metals like lead in the ground. Sometimes it is difficult to determine if the manufacturer is a GMP company, because your are purchasing the product from the distributor, not the manufacturer. Several manufacturers claim superior absorption, but it is important to view the data used to make these conclusions. Typically these data show detection of increased glucuronidated (tagged for removal by the kidneys are limited penetration to the brain) but do not assess untagged curcumin, which is permeable to the brain. In other words,data demonstrating superior absorption as measured by liver-tagged curcumin poorly predicts levels achieved in the brain. In contrast, untagged or free curcumin readily penetrates the brain and free curcumin levels in the blood correlate positively with levels in the brain in animal studies. Dr. Frautschy received a National Institute of Health drug development grant U01AG028583 a Drug Development grant to develop a formulation of curcumin that can be taken orally and penetrate the brain. This led to development of a solid lipid particle formulation of curcumin patented by UC Regents and Veteran's Affairs and licensed to Verdure Sciences as Longvida. Each capsule is 500 mg (125 mg of curcumin). Verdure Sciences is certifed for Good Manufacturing Practice, ensuring the absence of toxic metals and using organically grown turmeric. DiSilvestro et.al., at Ohio State University found that the Longvida curcumin formulation reduced plasma levels of beta-amyloid as well as cholesterol and markers of inflammation in plasma of 40-60 year old subjects.
We are now conducting a clinical trial to determine Longvida's effects in subjects at risk for Alzheimer's.
How much curcumin should I take?
The short answer is 'we do not know the dose needed'. The answer to this question will also depend on how you take it, if you take it on an empty stomach, whether you dissolve it or not and whether and how it is formulated. Unlike drugs, one cannot determine the dose needed for curcumin unless one knows the tissue levels achieved for that formulation. Clinical trials for each each disease and each stage and each formulation would need to be conducted to identify effective tissue levels and that information will be needed to be able to recommend required dosing. In animals levels of 0.6 micromolar are sufficient to reduce amyloid pathology. If effective for prevention and treatment of MCI and Alzheimer's, the dose required may depend on stage. Extrapolation from animals studies suggest that a range of 4-8 capsules of 500 mg Longvida (125 mg of curcumin) per day may be efficacious; however the dose for prevention may be much less, even 80 mg/day, as suggested in the Ohio State University study If effective for prevention, treatment of MCI, treatment of Alzheimer's, the dose required may depend on stage. A published study from DiSilvestro et al. at Ohio State University, showed daily intake of 80 curcumin from Longvida reduced plasma levels of beta-amyloid as well as cholesterol and markers of inflammation plasma in subjects 40-60 years old.
Extensive toxicology conducted by the National Toxicology Program demonstrated that turmeric oleoresin (80% curcumin) is safe. As described in Title 21, Section 182.20 turmeric oleoresin is listed as one of the oils or oleoresins in plants as generally recognized as safe (GRAS) FDA's GRAS list. The European Food Safety Commission (EU), which has stricter requirements than the FDA for food safety, has also designated curcumin as safe.
However formulations that increase the free form also need to be tested for safety. Longvida Toxicity studies on Longvida find similar safety as compared to unformulated curcumin.
We are conducting a clinical trial to determine if Longvida is effective in Mild Cognitive Impairment on Brain Glucose Metabolism and Inflammatory Biomarkers. We have chosen s dose based on extrapolation from animal studies based on doses needed for neuroprotection and neuro anti-inflammatory properties testing whether 8 capsules daily may be sufficient. As with any drug, it is recommended to titer up to a dose slowly (1-2 capsules daily) then 2-4 capsules 2nd week and so on. Dose may depend 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 or white blood cell (Buffy Coat) levels of free curcumin parallel brain levels, but not necessarily plasma levels, as plasma levels can be non-detectable when brain levels are high (Begum et al). It has a very short half life in plasma but a very long half life in brain because it is lipophilic (fat-loving) corresponding to its much higher concentrations in the fatty brain tissue than in blood.
When in relation to a meal should I take curcumin to limit its metabolism?
Fasting improves free curcumin absorption (eg. minimum of 3 hours after a meal). You make take it with a small drink (4-6 ounces; eg. cherry juice with a higher pH making it more soluble. Wait an hour before eating a meal. HOWEVER, ancectodal evidence suggests that some people may have sleep disturbances if taken before bedtime.
How will I know if curcumin is working?
Since there is no trial demonstrating effectiveness of curcumin in preventing Alzheimer's, we don't know how to answer this question until the trials have been conducted and completed. Anecdotal evidence suggests that slowly titering up and conducting self-administered memory tests can be helfpul in determining if it is helpful and at what dose. Some people use solitaire to monitor improvements. There maybe also be online tests to document memory changes. Since it takes 10 days to build up levels of curcumin in tissues, it may be important to titer up or down at 10 day intervals.
An immediate effect on memory has been describe anectdotally, but it would not necessarily be expected. In mouse studies spatial memory was measured after three months treatment. The most obvious initial effect would be a reduction in symptoms of joint pain or other inflammatory conditions. In one trial described here, only unformulated curcumin was used and free curcumin was relatively undetectable. Importantly, in extended results from the naproxen trial for Alzheimer's prevention, naproxen showed prevention of conversion to Alzheimer's; however, during the first year subjects’ memory worsened. It has not yet been determined whether lowering the dose until symptoms subside might avoid these deteriorations. Considering that we know that in animals curcumin clears out toxic amyloid and tau aggregates, it could conceivably transiently worsen memory. Although transient worsening of memory has not been observed in animals, it has been anecdotally been reported by some patients.
If I am considering taking curcumin with other nutraceuticals, what cocktail can I take?
Animal studies suggest that curcumin and fish oil synergize. It is very difficult to identify the nutraceuticals that synergize and those that counteract each other. Therefore, when exploring nutraceuticals it is important to add one at a time, for example at a minimum of 10-day intervals and monitor its effects.
Should I take DHA and curcumin together if I know I have the ApoE4 allele, making me at risk for Alzheimers? 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 would achieve a higher DHA to EPA ratio to avoid EPA competing for DHA incorporation into neuron membranes. The rationale for combining fish oil and DHA is that fish oil contains EPA, which may reduce risk for cardiovascular disease.
600-900 mg of DHA is recommended. 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.
Press Release: University of California – Los Angeles, January 23, 2018.
Daily consumption of a certain form of curcumin — the substance that gives Indian curry its bright color — improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers.
The research, published online Jan. 19 in the American Journal of Geriatric Psychiatry, examined the effects of an easily absorbed curcumin supplement on memory performance in people without dementia, as well as curcumin’s potential impact on the microscopic plaques and tangles in the brains of people with Alzheimer’s disease.
Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer’s disease and better cognitive performance.
“Exactly how curcumin exerts its effects is not certain, but it may be due to its ability to reduce brain inflammation, which has been linked to both Alzheimer’s disease and major depression,” said Dr. Gary Small, director of geriatric psychiatry at UCLA’s Longevity Center and of the geriatric psychiatry division at the Semel Institute for Neuroscience and Human Behavior at UCLA, and the study’s first author.
The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.
All 40 subjects received standardized cognitive assessments at the start of the study and at six-month intervals, and monitoring of curcumin levels in their blood at the start of the study and after 18 months. Thirty of the volunteers underwent positron emission tomography, or PET scans, to determine the levels of amyloid and tau in their brains at the start of the study and after 18 months.
The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.
The amygdala and hypothalamus are regions of the brain that control several memory and emotional functions.
Four people taking curcumin, and two taking placebos, experienced mild side effects such as abdominal pain and nausea.
The researchers plan to conduct a follow-up study with a larger number of people. That study will include some people with mild depression so the scientists can explore whether curcumin also has antidepressant effects. The larger sample also would allow them to analyze whether curcumin’s memory-enhancing effects vary according to people’s genetic risk for Alzheimer’s, their age or the extent of their cognitive problems.
“These results suggest that taking this relatively safe form of curcumin could provide meaningful cognitive benefits over the years,” said Small, UCLA’s Parlow-Solomon Professor on Aging.
Journal Reference: Gary W. Small, Prabha Siddarth, Zhaoping Li, Karen J. Miller, Linda Ercoli, Natacha D. Emerson, Jacqueline Martinez, Koon-Pong Wong, Jie Liu, David A. Merrill, Stephen T. Chen, Susanne M. Henning, Nagichettiar Satyamurthy, Sung-Cheng Huang, David Heber, Jorge R. Barrio. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. The American Journal of Geriatric Psychiatry, 2017; DOI: 10.1016/j.jagp.2017.10.010
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