Description

Background Moderately high readings for serum TG have been thought to place many people at risk for cardiovascular disease (CVD) and other problems. However, for a few years, doubts were expressed about high TG as an independent risk factor for CVD and maybe other problems in most people. More recently, the tide has begun to turn back due to new studies and new attention to old studies. Now, TG readings are again being thought to affect vulnerability to CVD, fatty liver, high blood sugar, and other problems including general inflammation. Some of these studies have shown evidence that TG effects can be independent of LDL or total cholesterol readings. Also, one of these studies suggest that even dropping TG readings from the top of the normal range to lower values can produce benefits.

People with TG readings between the top of the normal range to moderately high usually do not take drugs to lower TG values. Therefore, a need exists for cost effective, low side effect alternatives to help maintain normal TG readings. Nutritional supplements could fit in here. The Dietary Supplement and Education Act (DSHEA) allows for structure function claims of helping maintain blood lipids in the normal range. Low level general inflammation, which falls below what's seen with inflammatory diseases or injury, can also raise the risk for many health problems. Drugs are not generally employed to minimize this type of inflammation. So, as with moderately high TG readings, relatively safe and inexpensive non-drug alternatives can be sought (including nutritional supplements).

This researcher has found that under certain conditions, two natural ingredients each lower TG readings. One ingredient is a high absorption form of curcumin extract from the spice turmeric (Longvida Optimized Curcumin®). A dose of 400 mg per day (80 mg curcumin) lowered TG levels in healthy middle aged women. Aanother group has found that a third ingredient, astaxanthin can produce a substantial drop in TG values. A dose of 12 mg/day was more effective than 6 mg but the same as 18 mg. Also of note, readings for HDL cholesterol, the so called good cholesterol, rose a little. Another astaxanthin study found a drop in TG values in people with type 2 diabetes. A TG lowering effect of astaxanthin has also been seen in animal studies.

It's doubtful that any of these three ingredients could produce the really large TG drops needed by people with very high values. Even so, for people in the borderline to moderately high range, these ingredients, especially in combination, could help maintain normal range values.

Eventually, a combination product could be made of astaxanthin + Longvida Optimized Curcumin® + the third ingredient. However, there is work to be done before that can be considered. One lacking is that three ingredients have never been tried in combination. But, even before trying that, another issue must be addressed. For all three ingredients, the human research cited above have all been done in subjects whose TG readings were good to begin with. Therefore, it is not known how these ingredients, combined or individually, will affect TG readings in people with higher starting values.

On the inflammation side, both curcumin and astaxanthin are considered anti-inflammatory though a lot of disjointed data exists. A meta analysis exists for supplementation of curcumin and supplementation of astaxanthin in relation to c-reactive protein (CRP), a general marker of inflammation. Each analysis concluded that overall, CRP was decreased. However, some inconsistency existed in terms of results, types of subjects examined, doses, exact nature of the extracts, and co-treatments. The latter hold particular importance for curcumin, which was sometimes given with piperine, which can conceivably have its own effects (good and bad). Thus, a need exists to study this project's type of curcumin and astaxanthin at reasonable doses in a fairly broad population.

One possible anti-inflammatory mechanism of both astaxanthin and curcumin is elevation of body glutathione. This molecule can inhibit inflammation. This project will examine whole blood glutathione.

One body area where inflammation protection may be especially useful is the liver. Both curcumin and astaxanthin have shown protection against chemically induced liver injury in experimental animals. In addition, turmeric, the source of curcumin, has been used in Indian traditional medicine for treating liver problems. This researcher has found that in generic middle aged women without liver problems, Longvida lowered readings for alanine amino transferase or ALT. ALT is not a direct indicator of inflammation. However, liver inflammation can cause liver cell damage which leaks ALT into serum to elevate readings. The results obtained by this investigator need to be extended.

Hypothesis This proposed project tests the hypothesis that astaxanthin or Longvida supplementation will lower TG readings in people with normal to moderately high starting values. A secondary hypothesis is that the supplementation will raise HDL cholesterol readings and depress values for some markers of low level inflammation.

Methods Subjects will be adult males and females aged 21-59 that lack unstable health problems that can affect TG or systemic inflammation readings. Subjects in this project will have starting TG reading of 140-250 mg/dL. Initially, this eligibility will be based on eligibility questionnaire. However, if the initial blood draw finds TG readings outside the range, subjects will be excluded and replaced. Other discontinuations will be for a subject's decision or a change in health or medication disclosed by the subject to Medinutra. For these discontinuations, subjects will not be replaced. In the applicant's experience, no dropouts, or at most one, would be expected for this type of study.

For 6 weeks, subjects will take one of the following orally as one capsule/day (up to16 people/group):

Placebo (cellulose at a low dose) Astaxanthin at 12 mg/day-from BGG Longvida Optimized Curcumin® at 400 mg per day (80 mg curcumin)-from Verdure Sciences Longvida Optimized Curcumin® at 200 mg per day (40 mg curcumin)-from Verdure Sciences

The 80 mg curcumin dose is a standard amount for this product. The 40 mg dose is being tried as a step to determining the lowest dose that can produce benefits. The astaxanthin amount is based on a dose response study for TG effects. Blood will be drawn before and after the intervention by a Labcorp facility near the subjects' residence. Labcorp will do all the study analysis on the blood samples.

Neither Labcorp nor the study subjects will not know the assigned capsule identity. Thus, this will be double blinded and randomized in terms of the participants and analyzers

For each measure, for each of the treatment groups, pre- and post-treatment values will be compared by paired t-test. In addition, the changes in values for each supplement group will be compared to placebo by unpaired t-test. For non-normal distribution, nonparametric tests can be used. Also, each group will be compared to the others by ANOVA followed by Tukey analysis when applicable. Significance is set at p < 0.05 for all tests.

Subject numbers and power calculation This project is intended to see if further research is justified on certain wellness parameters in response to each of two supplements. Further research would be on the individual ingredients as well as the combination of both ingredients as well as these two ingredient + another ingredient. Justification for more work will only occur if substantial changes occur consistently. Therefore, a relatively small subject number should be sufficient to see such patterns. A power calculation was done for changes in serum TG levels for Longvida vs placebo. A previous study from this researcher got a 15% drop in people with low starting values. The percent change may be bigger in people with higher starting values, but the power calculation was done with 15%. Placebo was set at 2%. An upper end of SD for the changes is hypothesized at 8.5%. Using a power value of 0.95 and p = 0.01, 15 subjects are needed per group. Recruitment will shoot for 16 subjects to allow for 1 drop out per group. Dropouts should not occur much if at all. That's because participation is not demanding and subjects can't tell if a treatment is not "working."

Safety considerations. A safety review of astaxanthin says that natural versions are safe at doses equal or greater than the current project dose. This was based on 35 human studies. The FDA classifies curcumin as Generally Regarded as Safe (GRAS). The dose there is less than the higher dose in the current project, but only by 25%.

Despite this classification, and despite use of curcumin to treat liver problems, a few reports of curcumin-induced liver injury have been reported. To my knowledge, none have involved the form or dose of the current project. A survey was done on liver toxicity cases where a person was taking supplements of either curcumin or turmeric, the spice that contains curcumin. In 12 years, only 10 cases were found. The authors of the survey concede that not all the cases of liver toxicity could be definitely attributed to curcumin or turmeric.