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NutraOrigin's Omega-3 Fish Oil Shows Promise for Sleep Deprivation

White Paper 1: NutraOrigin

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Sleep loss has reached epidemic proportions in America over the past decades. We have a 24/7 work environment where shift work is common, and shifts in excess of eight hours are the norm. The results of sleep loss can be catastrophic, leading to workplace accidents and injuries, traffic accidents and other incidents that result in injury and/or loss of life. Most recently a lack of sleep (the young co-pilot had hopped flights from Washington to New Jersey, sleeping on a chair in the pilot's lounge in the 48 hours before the flight) contributed to the Continental Air Flight 3407 crash in February of 2009, resulting in the death of 50 passengers and crew. While this example is extreme, less than optimal sleep is common in the US and worldwide resulting in widespread negative consequences for health and quality of life. Sleep deprivation is associated with physical, physiological, cognitive, and psychological consequences, as well as increased risk for disease. Physically, these consequences include muscle fatigue and pain, reduced response times, and nausea. Physiologically, elevated inflammation, blood pressure, insulin and glucocorticoid resistance, and reduced wound healing can result from chronic sleep loss. Irritability, depression and poor impulse control and well as impaired reasoning and decision making, reduced accuracy, and longer reaction times are some of the psychological and cognitive symptoms associated with a lack of adequate sleep. Finally, chronic sleep deprivation (due to a lack of adequate sleep on a regular cumulative basis) is associated with diabetes, obesity, arthrosclerosis, heart disease, and even cancer.

How can we combat these consequences of sleep loss? The most obvious and well documented solution: sleep more. Napping has been found to be the most effective solution to combat sleep loss symptoms. But this is not always possible, as napping on the job is generally not acceptable. However, there is some indication that Omega-3 fatty acids (ω-3) might be able to reduce the effects. We know that increased intake of ω-3 are associated with improved neuro-cognitive development and functional retention with age. We also know that ω-3s are associated with improved sleep quality, improved mood, and an overall perception of improved quality of life. We therefore hypothesized that ω-3 would reduce some of the physiological, performance and mood effects associated with sleep deprivation.

In a recent independent study by the neuro-physiological monitoring specialists, Advanced Brain Monitoring, Inc (Carlsbad, CA), NutraOrigin's Omega-3 Fish Oil formula (1200 EPA/800 DHA) was compared to placebo (olive oil) in a within-subjects cross over design assessing neuro-physiological function and performance on repeated neuropsychological tests throughout a period of 24-48 hours of sleep deprivation. A sample of thirty subjects were asked to take either the NutraOrigin Omega-3 Fish oil or placebos for 4-6 weeks before undergoing laboratory controlled sleep deprivation of 48 hrs, followed by another period of 4-6 weeks in the opposite condition and a second 48 hr sleep deprivation period and assessment. Subjects took 2 pills with both the morning and evening meal to result in a daily dose of 4000 mg.

NutraOrigin's formulation was chosen for this study by Advanced Brain Monitoring, Inc after reviewing a large number of Omega-3 supplement options commercially available. The criteria used for selection of NutraOrigin's Omega-3 Fish Oil supplement included: EPA/DHA concentration, molecular distillation, and product stability. The concentration of EPA/DHA has been shown in many previous studies to play an important role in determining outcome effects, particularly neuro-cognitive effects. Lower concentrations are often ineffective. While lower concentrations can be compensated for by requiring intake of a larger number of pills, this is generally considered unpleasant. The second criterion, molecular distillation, was important for several reasons. First, molecular distillation reduces heavy metal contamination, reducing potential mercury poisoning and other concerns. Second, molecular distillation is associated with fewer digestive side effects, such as "fish burp" that are associated with taking fish oil supplements. When the available options were compared, NutraOrigin's Omega-3 Fish Oil supplement was the clear choice.

Neuro-cognitive assessments were made using the B-Alert wireless EEG 8+EKG system to collect performance synchronized EEG and EKG during a set of four-neuro-cognitive tests. The 3-Choice Vigilance Task (3C-VT) incorporates features of the most common measures of sustained attention, such as the Continuous Performance Test, Wilkinson Reaction Time, and the PVT-192, and it was designed to allow simultaneous monitoring and quantification of the EEG. The 3C-VT requires subjects to discriminate one primary (70%) from two secondary (30%) geometric shapes presented for 0.2 seconds over a 20-minute test period. A training period is provided prior to the start to minimize practice effects. The 3C-VT challenges the ability to sustain attention by increasing the inter-stimulus interval (ISI) across four, 5-minute quartiles. Subject's performance during the 3C-VT has proven sensitive to the effects of full and partial sleep deprivation in healthy subjects and to excessive daytime sleepiness in patients with Obstructive Sleep Apnea60-62. The 3CVT is followed by 5-minute Eyes Open (EO) and Eyes Closed (EC) with paced button press. EO presents a 10 cm circular image for 200 milliseconds in the center of the computer monitor, repeating every two seconds. Participants are instructed to press the space bar each time they see the image. For EC, an auditory tone every 2 seconds prompts participant to press the space bar. The final neuro-cognitive test is the Image Recognition and Memory Test (IR), evaluating attention, distractibility, encoding and image recognition memory. During the training phase, a group of 20 images are presented twice for encoding. The testing phase presents the 20 training images randomly interspersed with 80 additional images. Subjects must indicate whether or not the image was in the training set. Four equivalent image categories were used at random including: animals, food, sports, and travel. Outcome metrics for these tests include reaction time, inaccuracy (incorrect and missed responses), as well as EEG metrics of drowsiness and EKG based heart rate and heart rate variability. Heart rate variability is associated with autonomic nervous system activation; with low frequency power domination being associated with increased anxiety.

Subjects were also asked to rate their mood and perception of well-being and sleep quality with a series of subjective scales including the State-trait anxiety index, the center for epidemiological studies depression scale, the beck depression index, and the medical outcome scale- short form 36, and the Pittsburg sleep quality index.

RESULTS

Performance.
Both reaction time and inaccuracy were improved when subjects were on the NutraOrigin Fish Oil formula. Repeated ANOVA found a significant interaction of condition (Omega-3, Placebo) and time for both reaction time and inaccuracy metrics on the 3CVT task, F(8,528) = 2.54, p< .02 and F(8,528) = 2.71, p< .01, respectively and a main effect of condition was found for both metrics as well. These data are shown in Figure 1, and post-hoc analysis found NutraOrigin's Omega-3 Fish Oil supplemented subjects had significantly better reaction times and significantly less inaccuracy. SIR performances had a similar trend but were not significant across the two conditions (data not show, p=.07).

Figure 1. Reaction time and inaccuracy scores on the 3CVT task over time of sleep deprivation.
Significant post hoc comparisons are indicated with (*).

EEG indicators of drowsiness.
EEG based indications of drowsiness were also found to be significantly different over time through repeated ANOVA, for both 3CVT and SIR. While no condition X time interactions were found, a main effect for condition was shown for both tasks, Fs(1,508) ≥ 4.14, ps < .05, with NutraOrigin's Omega-3 Fish Oil reducing drowsiness overall, across the period of sleep deprivation (see Figure 2).

Figure 2. EEG based Drowsiness for 3CVT (left) and SIR (right) tasks.

Heart Rate Variability.
Low frequency power spectral density in the EKG signal was analyzed with repeated ANOVA. While no significant effects were found, a trend toward reduced low frequency power over time in the NutraOrigin's Omega-3 Fish Oil subjects compared to placebo treated subjects was shown. Greater low frequency power is associated with greater anxiety. Figure 3 presents these data.

Figure 3. EKG based Heart Rate Variability, low frequency power spectral data analysis
for 3CVT (left) and SIR (right) tasks.

Mood/Well Being.
Multiple assessments of mood were assessed, using ANOVA. ANOVA revealed no significant differences across conditions for the mood scales. However, a significant difference was shown (see Figure 4) in the perception of role capability related well-being, both emotional and physical.

Figure 4. MOS-36 scales for perception of physical and emotional role capability.

DISCUSSION

NutraOrigin's Omega-3 Fish Oil supplement effectively facilitated sleep deprived performance maintenance, reduced overall drowsiness, and improved perceptions of emotional and physical capability compared to placebo treated time points. In addition, it appears that NutraOrigin's Omega-3 Fish Oil was associated with a trend toward reduced signs of physiological anxiety. These very promising effects support the hypothesis that Omega-3 reduces the effects of sleep deprivation.

*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.