Vitamin A

Vitamin A as retinol from animal sources is vital to health. NIH Information listed here: ref

NOTE: Vitamin A and beta carotenes mentioned in the above reference studies often just use synthetic forms. The natural forms might overcome some of the negative toxic reactions linked to synthetic vitamin A supplements compared to the results from food source studies since they contain the same forms found in food while the synthetic form is missing critical elements. Read on.

Some studies have found that higher vitamin A levels interfere in bone health increasing fractures and also exhibit potential liver damage. ref Other research does not show this toxic effect from higher vitamin A, so there might be related nutrient levels that influence direction of action, or it could simply be a synthetic form that is at the heart of the toxicity. ref ref Since retinoic acid is involved in cell health, differentiation, metabolism, and cell death, it is important to get the proper amount for these activities but not tip into potential toxic reactions. Luckily, retinoic acid is effective against cancer at both low and high amounts, thus the potential for high amounts to turn toxic drives the necessity of lower dosages for prevention. ref 

NOTE: Vitamin A is from animal sources. The past low fat diets for cholesterol control and heart health were a disaster on the intake of vitamin A foods like cream, butter, and organ meats. Fish did get a boost. Plus, the changes to animal production, namely grain feedlots, also lowered the vitamin A content. Grass fed meats and organic dairy products will help increase natural vitamin A. 

Plants with carotenoids supply a preform of vitamin A. It takes six units of plant previtamin A to convert into one unit of animal source vitamin A. Beta carotene from plants can be split by the body into vitamin A as retinoic acid when needed. While animal source vitamin A as retinol can be converted into the retinoic acid, there might not be enough due to the diets that limit fat.

There are two receptors for retinoic acid, one derived from all-trans beta carotene and one from 9-cis beta carotene which divide into All-trans and 9-cis retinoic acids. While both can bind to and influence the retinoic acid receptors (RAR), it is only the 9-cis form that can bind with Retinoic X Receptors (RXR). The 9-cis RXR action is 10 times more effective than RAR action to prevent mutations of cells that can turn into cancers. Both all-trans and 9-cis must be present for these actions.

VITAL: Copied here is one of the retinol functions of RXR combining with hormone vitamin D receptor to influence organs. "1,25(OH)2D3 acts mainly through binding to its nuclear receptor, the VDR. The VDR interacts with the retinoid X receptor (RXR), forming a VDR-RXR hetero-complex, by which VDR acts as transcription factor able to bind to vitamin D-responsive elements (VDREs) in the promoter region of target genes (13)."  The synthetic beta carotene form of all-trans would not directly participate in this action.** Simply, vitamin D attaches to Vitamin D receptor which then combines with 9-cis RA receptor RXR and together they work with DNA to build vital proteins for the positive bone actions attributed to vitamin D, and other areas as well. see copy below too ref

Does it make any sense to only use synthetic all-trans beta carotene in over 90% of multiple-vitamins when the simple addition of D. Salina algae can supply BOTH all-trans and 9-cis beta carotene forms together in their NATURAL state? Since a balance of actions exists between all-trans and 9-cis, this one vitamin improvement could have a meaningful impact on health. article

**NOTE: The body recognized the importance of all-trans in many areas of actions, but for vitamin D gene influence, the 9-cis form is essential. It is interesting to note that 9-cis beta carotene will form both 9-cis retinoic acid as well as all-trans retinoic acid at about a 50-50% level. ref The all-trans beta carotene has only been found to convert 99% into all-trans retinoic and 13-cis retinoic acids. The exact mechanism is not yet understood, It is also not sure if all-trans will convert to 9-cis forms. Some does, but amounts notyet determined. The importance of a balance between all-trans and 9-cis is necessary for proper cell differentiation where dysfunction could result in as a potential cancer producer. While this study was in animals, further science shows actions similar in humans.

FYI: Of course, it is sometimes not logical to understand how or why nature works. All-trans is by far the most stable and active retinol form in the body. The 9-cis forms disappear with greater speed. But this does not mean they are not important. This is similar to the rather significant mistake scientists made with vitamin E forms when only d'alpha tocopherol was still found in blood plasma after a few days. The reason known now is that this form has a transporter protein to hold it there. The body has greater antioxidant needs where oxygen abounds at greater levels.

VITAMIN A IS NEEDED BEFORE VITAMIN D WORKS 

Copied here due to the importance of this interaction, the reference listed at end of VITAL: 

Biomed Res Int. 2018 May 22;2018:9276380. doi: 10.1155/2018/9276380. eCollection 2018.

The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health.

Khammissa RAG1, Fourie J1, Motswaledi MH2, Ballyram R1, Lemmer J1, Feller L1.    Author information 

Abstract

Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes (SKIN CELLS). 1,25(OH)2D, the biologically active form of vitamin D, exerts most of its functions through the almost universally distributed nuclear vitamin D receptor (VDR). Upon stimulation by 1,25(OH)2D, VDR forms a heterodimer with the retinoid X receptor (RXR) (FROM 9-CIS BETA CAROTENE converting to 9-CIS RETINOIC ACID FORMING RXR)( <These are forms of vitamin A). In turn, VDR/RXR binds to DNA sequences termed vitamin D response elements in target genes, regulating gene transcription. In order to exert its biological effects, VDR signalling interacts with other intracellular signalling pathways. In some cases 1,25(OH)2D exerts its biological effects without regulating either gene expression or protein synthesis. Although the regulatory role of vitamin D in many biological processes is well documented, there is not enough evidence to support the therapeutic use of vitamin D supplementation in the prevention or treatment of infectious, immunoinflammatory, or hyperproliferative disorders. In this review we highlight the effects of 1,25(OH)2D on bone and calcium homeostasis, on cancer, and refer to its effects on the cardiovascular and immune systems.

PMID: 29951549   PMCID: PMC5987305   DOI: 10.1155/2018/9276380

Remember that the synthetic from of beta carotene, ALL-TRANS, only or mostly forms into the RAR receptor while the 9-cis beta carotene (after converting into vitamin A retinoi acid) forms with both RAR and RXR receptors. These receptors have polar opposite combining attractions and this is why only the RXR mainly participates and forms with the vitamin D receptor, VDR, to stimulate DNA into supplying the elements necessary for bone building, etc. 

DO NOT PICK MULTIPLE VITAMINS WITH only SYNTHETIC BETA CAROTENE. Even some whole food multiple vitamins may not have both forms. Usually there is not enough information on labels to clarify what forms are present and when present if at a significant amount. Look for Dunaliella salina algae on label. The trade names like Betatene that use natural source D. salina algae offer various percentage products, so the exact amount of active elements may be difficult to determine.