Our NLR results

The importance of copper in the function of neutrophils and lymphocytes as been addressed on another post. This post never actually presented real data. We retrospectively analyzed data from a study performed by KGK Synergize in 2014. KGK analyzed the raw numbers of neutrophils and lymphocytes using an ANOVA model because the data were nonparametric. This post presents how we analyzed data collected by our CRO that has be registered at https://clinicaltrials.gov/ct2/show/NCT04737278. The graphs sort of tell their own story. Until FDA gives the green light, we are making no medical claims.

This free stats site uses six different sets for normality:  Shapiro-Wilk, Shapiro-Francia, D’Agostino-Pearson, Jarque-Bera, Cramer-von Mises, Anderson-Darling.  The sensitivity was set at p<0.05. 

Given these results, it was decided to skip the ANCOVA in favor of ANOVA since the assumption of normality is met for NLR data.  Went back and checked the neutrophil counts.  Very definitely not a normal distribution.

 Placebo1Placebo2Placebo3Cu 1Cu2Cu3
Minimum1.1428570.95833310.6190480.6250.766667
Maximum3.7272734.154.6666674.63.833333
Sum55.5898253.2932561.5224549.6553549.6677245.39949
Points282828282828
Mean1.9853511.903332.197231.7734051.7738471.62141
Median1.7571431.7450982.0416671.6666671.751.439103
RMS2.0919882.0168282.4106441.9618781.9273151.758534
Std Deviation0.671490.6792691.0098540.8544420.7674950.693279
Variance0.4508990.4614071.0198050.7300720.5890480.480636
Std Error0.12690.128370.1908440.1614740.1450430.131017
Skewness1.2840531.2711231.4408431.7563521.6418781.399153
Kurtosis0.9203681.9879521.7941573.6315114.6852512.016536
normalityPass allPass 1st 4Pass allPass allPass allPass all
Placebo1-3 are NLR ratios on clinic visits 1-3 for the placebo group. Cu1-3 are NLR ratios for the Cu(I)NA2 group for clinic visits 1-3.

Having proven normal distribution another free stats website was used to perform ANOVA. A free site was used for 2-way ANOVA.

ANOVA Summary     
SourceSSdfMSFp
visits0.4110.410.650.422
treatments3.2613.265.140.025
visits x treatments1.3111.312.070.153
Error66.571050.63  
Total71.55108   
A table of Anova values from teh free website. Note that only the treatment term is significant.
 PlaceboCu(I)NA2P Value
Mean ± SD (N) Median (Min – Max) Mean ± SD (N) Median (Min – Max)
   Neutrophils (109/L)
Screening3.49 ± 1.12 (28)
3.4 (1.8 – 6.4)
3.45 ± 1.16 (28)
3.2 (1.3 – 6.3)
Baseline3.35 ± 1.13 (28)
3.1 (1.5 – 6.2)
3.28 ± 1.06 (28)
3.15 (1 – 6)
Visit 3 (Day 28)3.60 ± 1.13 (27)
3.6 (1.7 – 6.4)
3.15 ± 1.19 (26)
2.85 (1.5 – 7.2)
0.03*
Change from Baseline to Visit 30.32 ± 0.83 (27)
0.2 (-0.8 – 3.6)
 p = 0.05§
-0.13 ± 0.73 (26)
0.05 (-1.9 – 1.2)
 p = 0.38§
    –
Lymphocytes (109/L)
Screening1.84 ± 0.51 (28)
1.9 (0.8 – 2.8)
2.15 ± 0.69 (28)
2.15 (0.6 – 3.4)
Baseline1.83 ± 0.51 (28)
1.8 (0.9 – 2.7)
2.01 ± 0.64 (28)
1.9 (0.5 – 3.2)
Visit 3 (Day 28)1.74 ± 0.51 (27)
1.8 (0.9 – 2.6)
2.04 ± 0.72 (26)
2 (0.6 – 3.4)
<0.01*
Change from Baseline to Visit 3-0.08 ± 0.34 (27)
0 (-0.8 – 0.4)
 p = 0.22§
0.03 ± 0.39 (26)
0.1 (-0.8 – 1)
 p = 0.73§
Neutrophil to lymphocyte ratio
Screening1.99 ± 0.67 1.76 (1.14-3.72)1.77 ± 0.85 1.67 (0.62-4.57) 
Baseline1.90 ± 0.68 1.75 (0.96-4.1)1.77± 0.77 1.75 (0.625-4.6)p=0.44§  
Visit 3 (Day 28)2.20 ± 1.03 2.08 (1.0-5.0) p=0.066§1.62 ± 0.69 1.44 (0.77-3.83) p=0.054§p=0.03
Change from Baseline to Visit 3-0.294 ± 0.813 -0.049 -3.38 to  1.380.152 ± 0.400 0.123     -0.625 to 0.902  p<0.05§  
Table 3 Changes in white blood cell populations indicative of inflammatory status.  *Between group comparisons were made using ANCOVA.    §Within group comparisons were made using the paired Student t-test.  Probability values ≤0.05 are statistically significant. ∆ 2 way ANOVA treatment effect   Note change from baseline to visit 3 is positive if there is a decrease in the cell count or a decrease in the ratio.

Note that a change in baseline to Visit 3 is the baseline value minus the Visit 3 value. A The mean change in baseline to visit 3 decreased in the placebo group meaning that the NLR increased in the placebo group.

Examples of Cu(I)NA2 helping those that are..

Mitosynergy has a conviction that customers that are worse off have the most symptom improvement. This multiple regression model provides preliminary statistical backing for this conviction. The red line of “manuscript in preparation Figure 4A illustrates what one would see if there was no improvement of the baseline score on the X-axis to the score on day 28 on the Y-axis. The slope would be 1.0. The equation of a line documenting a complete “cure” would have a slope of 0 and and a Y-intercept of 0 to 1. The placebo slopes were about 0.65, close enough to 1.0. The slopes of theCu(I)NA2 line for the females was less than 0, -0.17. Examination of the NLR will reveal a different phenomenon.

Figure 4 (a manuscript in progress) Exemplary graphs from SQIR questions A. Symptom Domain, pain. In females the probability is higher that the Cunermuspir and placebo lines have different slopes (p=0.037). In males the probability that the lines have different slopes did not meet the threshold of significance. Red lines indicate the slope of 1.0, or no change in the score from baseline to day 28. B. Impact Domain, overwhelm by symptoms. C. Function Domain, lifting bags of groceries. For both males and females the slopes of the Cunermuspir and placebo lines are different at p=0.0114 and p= 0.0043, respectively.


A graphical view of the NLR




Figure 5 Neutrophils, lymphocytes, and the neutrophil /lymphocyte ratios: the amount on day 28 as a function of baseline, day 1.


Male and female data were combined when analyzing neutrophil and lymphocyte counts because separating the data did not reveal any difference. Population variations are very apparent when the data are presented graphically. The interesting phenomenon is that the slopes of the lines of the placebo and Cu(I)NA2 were statistically the same. The y-intercepts appear to be different. While these small studies are to be interpreted with caution, Cu(I)NA2 seems to improve the NLR ratio for all the participants a little.

Published by BL

I like to write educational websites

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