Oxygen, Astaxanthin and CBD

By John Carberry

The FDA very closely monitors the publication of “claims” associated with products being sold to the public. For instance, while we have strong evidence of bioavailability and efficacy of CBD and astaxanthin prepared optimally, it will take years to do the expensive studies that will allow us to make FDA approved “claims”. While this is good and necessary for the public good and protection, the accumulation of clinical data, models, scientific findings and data is a long-term process and the public can benefit from seeing its progress.

Five hundred million years ago the oxygen content on Earth was as much as 35%. Today it is 21%. Oxygen is necessary for biological operations; it is the source of our energy. Over time our biological systems have created many methods to control oxidation stress, oxidative stress, particularly from “free Radicals” where an oxygen has an extra electron. These are often called “Reactive Oxidative Species”.  Our health demands we address oxidative stress.

In this essay I will strive to explain why and how an optimal supplement could be a DHA EPA rich oil carrying very bioavailable CBD, Astaxanthin and Chlorophyll.

One of our biological systems is the eicosanoid system, more than 150 eicosanoids have been identified, and they are made and used instantly. Key inputs to this system which makes and uses these important signalers instantly are omega 3 and omega 6 fatty acids, arachidonic acid (AA) and strangely enough, CBD. CBD does not have much affinity or interact much with the CB1 and CB2 receptors. CB1 receptors are abundant in brain and nervous system while CB2 receptors are mostly expressed immune and endocrinal infrastructure. Recent literature makes it clear that CBD is a very powerful agent to release AA and this may indeed be its main functional value. And of course, CBD is made de novo in our biological operations. All these things and more are very vulnerable to oxidative stress. So in addition to the omega 3 and 6, the AA and the CBD, a strong antioxidant process is necessary for our health. It must be dietary and available in our diet.

Oxidative stress happens in many states and cases. When an inflammatory event is under way it is often caused by detection of unwanted antigens. An insult to the organism, it can be an injury or an infection, local or global, will normally result in a “storm” of eicosanoid activity to attack the invasion and put it down. This is triggered mostly by a rise of those antigens, often on the surface of cells in the organism which it recognizes as nonnative.

This is very well described in Eicosanoid Storm in Infection and Inflammation by Edward A. Dennis and Paul C. Norris published in Nat Rev Immunol. 2015 August; 15(8): 511–523. doi:10.1038/nri3859.

There are two parts of this “storm”. The inflammatory normally comes first and it should be succeeded by a “resolving” or “resolution” phase. This second phase is normally characterized by strong anti-inflammatory activity.  An ongoing supply of AA is required to sustain this “storm” through the first and second phase.

There is also ongoing oxidative stress due to the rise and presence of reactive oxidative species (ROS), where in a nice presence of anti-oxidants is desired. Astaxanthin, which tends to find and take up residence in the cell plasma membrane, fills this function very well. This is described below by Ranga Rao Ambati et. al.  in their paper Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review published in Mar. Drugs 2014, 12, 128-152; doi:10.3390/md12010128 

Figure 4. Superior position of astaxanthin in the cell membrane [12].

 

The astaxanthin is hydrophobic, does not like water. It likes oils and lipids. Once it gets to a plasma membrane is it likely to stay there. This is why astaxanthin builds up in the cells and tissues, and why it is so powerful to pull ROS out of the cell and move it to a Vitamin C.

In her paper Evolution of dietary antioxidants Iris F.F. Benzie of the Ageing and Health Section, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong, published SAR, China Received 26 June 2002; received in revised form 15 November 2002; accepted 2 December 2002 considers the questions relating to our evolutionary dietary intake of antioxidants and their bioavailability before and after the industrialization of food production. The industrialization of food production resulted in significant reductions of dietary antioxidants. To achieve good health, we need to address these needs. Here we learn our diets changed, the amount of dietary antioxidants were dramatically reduced, and to be healthy we need to supplement.

 

 

Table 1

Estimated daily intake of selected nutrients in Paleolithic and modern diets

Micronutrient	Paleolithic	Modern	Current day average requirement
	diet	diet	or recommended allowance
Vitamin C (mg)	604	59–115	30 (UK) 75–100 (women); 90 (men) (US)
Vitamin E (mg)	33	5.2–6.0	7 (UK); 15 (US)
Folate (mg)	357	208–317	140
Carotenoids (mg)	5560	1846–2048	Currently no recommended allowance
Iron (mg)	87	9.5–17.2	7–10
Copper (mg)	?	1–1.3	0.8
Zinc (mg)	43	7.1–13.6	5.5–7.5

Data from Eaton et al. (1997), Carr and Frei (1999), Kiely et al. (2001) and Levine et al. (2001).

Here Dr. Benzie cites a variety of sources to look at dietary antioxidants and their bioavailability and concentrations in human plasma:

One of the puzzles in primate evolution is the loss of primates of the power to make vitamin C de novo as do most all other mammals and reptiles. Vitamin C is an important antioxidant and precursor also for making collagen.

Mammals make vitamin C de novo in the liver, reptiles make it in the kidney. Dr. Benzie explains that for the most part evolution is a matter of economics and that there must be a balance in the economic equation with regard to natural selection. So, we lost the ability to make vitamin C, but not the critical need to have it. It must be that our dietary intake satisfied our need for this critical antioxidant:

 The antioxidant operation in healthy biological operations is very complex and involve many players. Vitamin C is water soluble and easily eliminated within several hours. It is believed that it can carry away ROS conveyed from inside the cell to the outside by astaxanthin. In Dr. Ambati’s figure 4 above this is clearly illustrated.

The antioxidant system must protect many processes and systems and constituents from ROS if the organism is to enjoy good health and operations.

One of the things we focus on at Sustainable Aquatics, the founder of Sustainable Nutrition and SNCE Laboratories, is the importance of bioavailability and the impact of antioxidants, nutrients, macro, micro and nano nutrients.

We were excited to read Dr. Meor Mohd’s Enhanced Oral Bioavailability of Astaxanthin with Droplet Size Reduction M.M.R. Meor Mohd et. al. Food Sci. Technol. Res., 18 (4), 549–554, 2012 for the reason that it reinforced work we had done here at SA with regard to nano sizing and bio availability. In particular we have focused on astaxanthin, chlorophyll, CBD and the beneficial use of fatty acids as well. Dr. Meor Mohd reported the following data:

Fig. 1.  Rat plasma concentration versus time profile of nanosized emulsion, macro sized emulsion and oil solution of astaxanthin after oral administration of 80 mg/kg astaxanthin formulation (n = 9).

 Table 3.  Individual numerical value of C_max, T_max and. of three types of formulation tested on nine. Individual numerical value of C_max, T_max and AUC_0‒∞. of three types of formulation tested on nine.

	Oil Solution			Macro Sized Emulsion			Nanosized Emulsion
	Cmax	Tmax	AUC0‒∞	Cmax	Tmax	AUC0‒∞	Cmax	Tmax	AUC0‒∞
	ng/mL	(h)	(h.ng.mL	ng/mL	(h)	(h.ng.mL	ng/mL	(h)	(h.ng.mL
1	325.08	5.00	11302.8	499.6	4.0	17719.5	697.08	3.0	20731.8
2	330.16	4.00	13563.8	429.55	4.0	16587.4	653.33	2.0	25505.3
3	315.76	5.00	6804.7	429.55	4.0	12349.3	640.84	2.0	24732.2
4	311.61	5.00	11037.7	403.74	4.0	14214.2	732.93	3.0	13251.2
5	309.4	6.00	14204.4	437.39	5.0	15137.5	682.69	4.0	15671.2
6	294.92	6.00	10702.2	497.28	4.0	16201.5	746.32	3.0	16383.3
7	330.01	6.00	10910.7	459.73	5.0	16977	694.47	3.0	26937.6
8	301.36	6.00	1456.05	531.82	4.0	16587.5	751.51	2.0	24931.8
9	301.91	6.00	10175.9	497.22	5.0	16931.2	689.22	3.0	17482.1
	313.36	5.44	10017.58	465.10	4.33	15856.14	698.71	2.78	20625.17

 

This footed very well with much of our own work, though our own work is measured by more visual and tangible results. For instance, we have learned that when fish make eggs it is a very rapid almost violent process which takes place often in just a few hours. The ovaries signal that they are going to be dividing cysts and will need yolk material, which is called vitellogenin.  (VTG). This message is picked up by the thyroid which makes a series of seleno proteins, three in particular, and these are issued by the thyroid and picked up by the liver which then uses them to make VTG and issue it so it is picked up in the ovaries, and in the case of marine teleosts, hydrolyzed, and built into yolk. So it is a rapid and almost violent process which requires the endocrinal and supporting systems to be working at top efficiency.

We believe that in nature marine fish eat a diet rich in antioxidants, including astaxanthin. So, we supplement our fish feeds with astaxanthin. Synthetic astaxanthin and from yeast does not work well for us at all. And from Haematoccocus pluvialis we have to nano size it. Here are pictures of blue tang eggs about 18 hours after fertilization, about a few hours from hatching using astaxanthin reduced in size from 50-micron cysts to 3-5-micron cysts by super critical carbon dioxide extraction and nano sized astaxanthin by SN’s process combined with pharmaceutical grade cod liver oil:

 

SCCO2 Asta blue tang eggs                           SN nano sized Asta blue tang eggs

 

SN’s astaxanthin is nano sized, we use very high energy in warm ethanol to not just extract the astaxanthin, but to break the encysted astaxanthin molecules down to nano sized molecule couples. At about 70 C in food grade ethanol we rotate stirring bars at 1240 feet per minute tip speed in 3 mm hard balls. Within ten to twenty minutes the dis-encystment is complete. This difference in bio availability can be seen in the dramatic increase in eggs, and egg yolk mass.

We have seen this difference in other studies. For instance, in rotifers fed a food including astaxanthin, the two types of astaxanthin showed a remarkable difference in reaction to Juglone stress. Juglone is a chemical used to present oxidative stress to measure reaction and resistance to oxidative stress:

We also looked at the effect in terms of amplification of populations of rotifers, fecundity:

All this seems to present strong evidence that bioavailability in fatty acids, in bio mass, and nanosized is much enhanced and much enhances many biological operations.

In each of these cases we observe that the endocrinal and other systems when liberated from oxidative stress operate at much higher efficiency, quickly measured in clear metrics.

From the literature we have concluded that CBD is much more a part of the eicosanoid system than the endocannabinoid system (ECS). Or that the ECS system is very much a part of the eicosanoid system. CBD does not couple with the CB1 or CB2 receptors. But it does release arachidonic acid from the phospholipids where they are stored. From Wikipedia:

Pathways in biosynthesis of eicosanoids from arachidonic acid: there are parallel paths from EPA & DGLA.

Our conclusions:

• We need vitamin C but we Homo sapiens, among the rest of the primates, stopped making vitamin C De Novo in our liver a long time ago, even though we very much still need it. It is probable when we stopped making it we could afford this energy saving change because our diet was rich enough in different valuable antioxidants;

• Astaxanthin was likely rich enough in our regular diet. We accumulated it in our cell structures and it offered protection against ROS, including protecting other systems.

• The eicosanoid system has more than 150 types of eicosanoid types and half of them can be said to be inflammatory and half anti-inflammatory.

• A healthy eicosanoid balance of omega 3 and omega 6 fatty acids is about 1:3;

 

• CBD is made De Novo but we also can supplement it, and it is an important player in the eicosanoid system in its ability to supply the arachidonic acid required to make the eicosanoids that are made and used instantly.

• Understanding how CBD plays such an important role in the eicosanoid system across most all the eicosanoids system, in a system with our normal modern diet challenged with excessive oxidative stress, explains how supplementation offers so much benefit across such a wide cross section of complaints;

• CBD and Astaxanthin become much more bio available when nanosized and presented in solution with fatty acids such as DHA and EPA.

• CBD and Astaxanthin are more powerful and more bioavailable when presented nano sized with constituents such as the Haematoccocus pluvialis bio mass, nano sized chlorophyll, other cannabinoids and the like.

• It is likely that astaxanthin takes up residence in the cell plasma membrane, the dimensions favor it leaving an ester group on either side of the membrane, and that the oxidative potential between the inside and outside of the cell would favor astaxanthin moving ROS from the inside of the cell to the outside of the cell;

• Where Vitamin C catches it and it is removed by the liver/kidney elimination system.

• Given the literature cited makes it clear we have dietary deficiencies in a wide range of antioxidants and given the evidence for bioavailability as a function of using fatty acids, nano sizing, nano sized bio mass, an optimal supplement might be cod liver oil rich in DHA, carrying nano sized astaxanthin, CBD and chlorophyll associated with their nano sized biomasses.