**Draft WIP / Work in progress Part 4 of 4**
**Undergoing writing & readibility amends December 2023**
** April-May 2024 Thoughts on exclusion and reinclusion**

Here in this Fourth and final part of this (work-in-progress) Self Meta ~ I conclude, with the following in mind:

• Conclusive thoughts on the opposition views to Vitamin D supplementation.
• Future subjectivity of this independent writeup. The need to advance further dialogues and self-research beyond the confines of this Self-Meta.
• Proposed cycling between various dosages. The need to consider cyclical dosages between none, low and high. Self-journal any sight of symptoms, and surrogate markers of wellbeing (eg. Quality of Life, digestion, metabolic profiling/glucose readings, mood, psychology, mental resiliency, fitness training records, etc). And;
• The need to consider Nutrigenomics profiling .To highlight if any disorders found in all logistics of Vitamin D metabolism pathways. This also include:
  • The need to consider any other profiling tests that may be of relevance including but not limited to:
    • Vitamin D nutrigenomics / including metabolism, and storage pathways.
    • Vitamin B  / methylation pathways.

Strictly WIP / work in progress. I would welcome any or all thoughts surrounding this initiative. 

Live-it-forward,

AW.

Discussion

The opposition to Vitamin D supplementation remains noteworthy for attentive individualisation, especially those who are affected with auto-immunity as implored by the opposition (Marshall, T. 2018). However, other confounders albeit lengthy to be included here for accessible reading, but to name a few surrounding supplementations that are widely considered complimentary and synergistic to Vitamin D's metabolism amidst alternative wellness, namely - Vitamin A, K2, magnesium ~ made this entire assumption that Vitamin D is harmful than it is protective somewhat difficult to accept. But This Author (AW) remains admissive that whilst he is not coming from an entirely academic background, there is much to be heard and/or to be understood from the merits of decreasing Vitamin D supplementation.

Nonetheless, in terms of reviewing from the studies on toxicity curated here thus far, there appears to be less, than there are substantial evidence/s for terminal side effects from supraphysiological (or beyond conventional) dosages.

Considering that from institutional finding, there is currently (to date) no consensus on what defines "Safe Upper Level" to Vitamin D (Amrein K. 2020). The Endocrine Society claims 10,000IU as the "Upper Daily Limit". But the European Food and Safety Authority recommends below 4000 IU per day.  Small studies (Heaney RP et al. 2003) seem to be in agreement that provided no underlying disorders Vitamin D supplementation in excess of 10,000  IU ~ per day ~ did not lead to adverse effects. 3,000 to 5,000 IU per day has been widely proclaimed as generally safe (Hollick, M. 2019).

Other topics that may prove  in regards to genetic polymorphisms remains sadly too complex and broad for general reading. However, these polymorphisms (or specifically ~ SNPs / single-nucleotide polymorphisms) may prove great importance for discerning readers to consult and pursue external nutrigenomics testing(s) on several other key groups of genes, enzymes and proteins profiling; from which Vitamin D metabolism from their inactive to active pathways are dependent. Hence ,nutrigenomic markers worth considering to test and sought full consultation so far are:

1. Vitamin B status and handling. Particularly Vitamin B12.
   1. Arguably anything that scrutinizes B12 may consequent / prompt the following connected markers ~ homocysteine handling, and overall methylation status.

April May 2024 Update: thoughts Vitamin D exclusion and reinclusion

Throughout the two months whilst writing the next Self-Meta on Vitamin A This Author (AW) decided to invest more time to determine effects if any, under Vitamin D depletion either abstaining all supplementation ¬ or ¬ supplementing with Vitamin A ¬ may produces any notable repercussions.

There is some degree of confidence that, despite not obvious at first few days ¬ that overall quality of life /QOL did, adversely decline in subtle but noticeable ways throughout the two months of :

1. Experimental increase of Vitamin A intake from bioavailable sources (DIY chicken liver pate) OVER Vitamin D. In other words, Vitamin A intake/supplementation: increase. Vitamin D intake/supplementation: decrease.
2. Reinclusion of Vitamin D supplementation (of 10k IU with K2). In other words,  Vitamin D intake / supplementation: increase. Vitamin A intake/supplementation : decrease

Chiefly among factors This Author(AW) felt compromised were : dry tired eyes / lack of moisture, overall stress resilience, sleep quality and psychological composure. These were noted when Vitamin D supplementation was drastically reduced whilst Vitamin A increased.

Firstly with eye health, those unaccustomed with Anklyosing Spondyltis (AS) is advised that any pinks or redness around the sclera (or whites of the eyes) may indicate sign of inflammation thought to be associated with the AS. A study reviewing eleven sources seem to indicate a correlation with lowered Vitamin D intake with severity of the disease. This Author (AW) has yet to find any suggestive workaround such a condition, he did however interestingly found that overall eye tiredness, but not its cosmetic redness seemed to be helped with increasing Vitamin D, OVER Vitamin A intake.

Stress resilience, sleep quality and composure wise also seem to indicate, throughout the two months update above; as supportive towards more Vitamin D intake and/or supplementation, over Vitamin A intake, specifically from bioavailable wholefoods (in This Author's preference and case ¬ Chicken liver pate DIY). Sleep quality seemed felt less in terms of overall rejuvenation, leading to noticeably increased sense of fatigues upon awakening  ,lingering hours on end until afternoons. Upon supplementing Vitamin D (10k IU per day) these effects seemed to decrease or lessen to a degree that is quite noticeable. Whether or not Vitamin A affects the complex cortisol / stress hormones dynamics remains a complex subject.

This two (months) of introspective exclusion and reinclusion is by no means a "defenitive" suggestion for prescribing complete elimination of Vitmain A sources. This Author (AW) believed that despite the markedly decrease QOL simply from manipulating Vitamin A:D (and vice versa) ratios from weeks cumulatively to these two month(s) ¬ is never to suggestthat Vitamin A has no utility. The copper content does nonetheless serve to regulate the immune system, and that arguably of equal importance - one of the most cost effective means of maintaining dietary choline status for overall methylation health, and support.

Nevertheless, readers should prompt for their ownselves enough time, should they likewise embark on similarly concentrated - exclusion and reinclusion surrounding Vitamin D to A ratio.

Course of Action (For Readers)

Following from above discussion, here the following course of action surrounding Nutrigenomics are proposed. For context, Nutrigenomics, or short for nutritional genomics is a branch of alternative medicine consultancy where DNA samples are taken, collected, and studied to highlight if any, mortality associations suggested by our most current available knowledge thus far surrounding Biochemistry, Nutrition and Epigenetics.

There are however factors to consider before readers may wish to undergo consulting:

1. Cost & accessibility. Nutrigenomics is a highly sought after consultancy; often requiring high financial investments amounting to at least hundreds of dollars. This investment, all of which is non refundable once a contract and consent is declared ~ goes towards:
   1. 1-to-1 initial and post (debriefing) consultations;
   2. DNA swab collection kit;
   3. Comprehensive genetic data interpretations and extrapolation(s) as interventions, and/or prelminary advices subject for further tests and/or investigations.
   4. Reports and results gathering ~ in writing.
2. Nuanced responsibility(s) for extrapolating all insights. To illustrate an example of a nutrigenomics package report; which below cannot be fully disclosed due to NDA / confidentiality courtesy usually anticipates surrounding:
   1. A  package of multiple genes testing (potentially dozens per report) ~ tailored to specific health goal or overarching concern (Autoimmune, food intolerance, exercise regiment(s), to name few).
   2. At least four (4) all the way to thirteen (13) or more reports detailing genomic interpretations based on the collected DNA.
   3. Each report provides biochemistry overview and implications on wider health and surrogate markers based on the summarised finding, if any - on the polymorphism found from the collected sample.

What genes should I test? A mini section on Nutrigenomics

There are select genes which may prove relevant or at least affecting in some way or another ~ to Vitamin D metabolism. Below is a list, although certainly not exhaustively complete at addressing these relevances as accordingly to several research sources  (Hu, Z et al. 2019),  (Tomei S. et al. 2020) and (Malloy PJ and Feldman D 2011):

1. 7-dehydrocholesterol reductase / NAD synthesise 1 (DHCR7/NADSYN1).
   Notable role and/or function(s): Conversion ~ in the early pathway (Skin)
2. Cytochrome P450 Family 2 (CYP2R1 and CYP27A1) . 
   Notable role and/or function(s): Conversion ~ in the early pathway (Skin>Liver)
   AND;
   Clearance ~ in the end stages (clearance and excretion of the active 1,25OHD) 
3. Cytochrome P450 Family 24 Subfamily A member 1 (CYP24A1). 
   Notable role and/or function(s): Self-adjust / control mechanism at preventing toxicity symptoms. 
4. 1-Alpha-hydroxylase (CYP27B1) 
   Notable role and/or function(s): Conversion ~ in the intermediary pathway (25OHD into active 1,25 OHD).
5. The Vitamin D Binding protein GC.
   Notable role and/or function(s): Transport ~mobilisation of the plasma 25OHD as well as the active 1,25OHD to various tissues.
6. The Vitamin D receptor
   Notable role and/or function(s): Reception / receivals (on all tissues) ~ the docking site which binds with the inactive plasma 25OHD as well as the active 1,25OHD. 

What about existing co-morbidities?

Unfortunately this Author (AW) cannot willingly indemnify any individuals whose conditions may already compel terminal care. Those with existing / monitored supervision on any supplementation would be wise to check with their physician prior to any decision making.

However, This Author (AW) nonetheless curates, that based from all literatures gathered thus far a number of co-morbidities, should they already afflict readers, would be wise to consult with their guiding physician before deciding whether to commence, increase or decrease ~ Vitamin D supplementation.  those who are diagnosed with Clinical kidney diseases (CKD), liver disorders, digestion or malabsorption disorders / gastric bypasses,  and existing heart disease should all prompt extra cautions when extrapolating this Self-Meta as overriding advices. As a kind reminder ~ nothing disclosed here is either definitive nor does it confide institutional overrides. These include (possibly):

1. Related minerals handling / metabolism disorders ~ particularly:
   1. calcium,
   2. magnesium,
   3. phosphate.*
2. Surrogate lifestyle markers ranging from most to least obvious ~
   1. sunlight exposure, dietary calcium intake, stress including environmental stressors from pollution.

*Phosphate in western diet and general food supply today is widely deeemed overly abundant. Thus many nutrigenomics practitioner may likely recommend reduced intake on a periodical on/off basis.

-- <WIP> --

Course of Action (Personal)

In light of the literatures presented in this Self-Meta This Author (AW) hereby propose under personal nuanced circumstance. Chiefly having considered the literatures he hereby:

1. Maintains view that Vitamin D; be it however deriving from food and/or sunlight source - remains an inseparable necessity for health maintenance.
2. Maintains supplementary intake of Vitamin D; as dosage ranging from at least higher than 2,000 IU per day to no more than repeated daily intake of 15K IU.
3. Maintains self-journalling, interest, research relative not confined to Vitamin D but anything else relative or appealing to; the auto immune condition AS (Ankylosing Spondylitis).

Future adjustments are likely necessary due to ageing cofactors & confounders. This Author (AW) believes cycling between high and low dosages remains warranted, at least as per seasonal basis and degrees of sun exposure. On summer ~ supplemental is likely reduced. Where as on winters ~ an increase. Maintenance dosages thus far hovers between 5,000 to 15,000 IU per day. This is also taken alongside (proclaimed) supporting  mediators against toxicity. Namely ~ Vitamins K2 (Mark(s) 4 and 7s), Magnesium and further co factors ~ Vitamin B6, Vitamin A and manganese. 

Conclusion

(WIP progress for readibility)

So far it remains difficult to extrapolate a course of action that is immediately applicable to all; without nuanced consideration(s) well and outside the indemnity of this Self-Meta. At best, personal nutrigenomics alongside guided interpretation with a geneticist or functional medicine practitioner would likely remain the best driver point of further discussion at determining appropriateness on high versus low dosages to defend against mortality markers.

Any arguments bearing from either side (both for and against supplementation) remains divisive in each of their own right despite seemingly extreme measures advocated ~ namely Coimbra Protocol versus that of those in favour of elimination of Vitamin D inputs, including whole food sources and sunlight. Any justification to adhere to these, both right down to the letter, and in long-term view ~ likely remains questionable. However all this remains a  matter of individual decision, and wherever justified ~genetic nuances that may warrant  highly personalised assistance as advised earlier ~ nutrigenomics profiling.

As an immediately accessible closing thought here is a question of pragmatism / practicality that hopefully warrants peaceful closure to Vitamin D toxicity debate. Abolishing anything that is holistic as "nature" already provides immediately through physics, ecology and thereby environment ~ be it sunlight or nutrient dense wholefoods ~ remains rightfully questionable.

For instance, avoiding foods rich with calcium and essential fats (eggs, fat-rich seafoods, shellfish, organ meats, dairy cheese) more than likely prompts overtime to becomes counterproductive given these foods more often than not contains nutrients that many modern food supplies typically lack. Namely, gelatinous amino acids,  and fat soluble bioavaiable vitamins ~ retinoid acid, COQ10, to name a few. However, far too many common fears ~  saturated fats chiefly amongst others that accompanying these foods for instance ~ remain semantically driven and institutionally enforced such that scientific inquiring becomes all the more challenging. If not ~ stigmatised in the name of statistical epidemiology (imposition of the average ~ on mass populace).

In light of the above, This Author (AW) generally agrees that at some point Nutrigenomics profiling is necessary for individuals to best determine all possible actionable points, on the basis of their own genomic profiling. Disadvantages, indeed remains possible, given that they are often costly, inaccessible to the general public, and certainly requiring more disciplined willingness, and responsibility for insight, much more than what is found and/or preached widely - amidst mainstream media.

Reciting as final course of action ~ This Author (AW) anecdotally still maintains a view for any supplement deemed both paradoxical harm and benefits ~ inclusions and exclusions together with self journalling still nevertheless prevails as his most pragmatic view. Exclusions and reinclusion here refers to cyclical dosaging between none, low and high - which, for as long as writing and accountancy is done so diligently ~ allows self-monitoring and reflecting on any effects and/or repercussions, if any, that follows inbetween these dosage ranges.

Thus, Vitamin D supplementation, whilst certainly justifiable for reduced supplementation in certain contexts (genetic inheritance abnormalities or certain autoimmune disorders) ~ still remains rightfully a nuanced and complex subject. Given that genetic errors are unavoidable in all of life's diversity, it is wise therefore for us all to deeply research and simultaneously should finances and accessibility allow ~ personal nutrigenomics for uncovering a more relevant insight.

In the meantime, This Self Meta unbiasedly concludes nevertheless that this is neither an overriding "clinical" advice or a casual suggestion to a broad audience. This is simply a personal and anecdotal initiative for  exercising self-academic curiosity(s) and scientific curation of cliff notes to further all dialogues between the known as well as the unknowns.

Thank you.

I, Andrew Wiguna / Author of this first (WIP/work-in-progress) Self-Meta wishes to thank however few readers to this concept initiative and by its presence of Youtube® channel to have read this Self-Meta either partially or holistically. Please share your thoughts and/or comments should you relate to any of these noteworthy food for thoughts.

Live-It-Forward,

AW.

July 1st 2022 First interim draft work in progress until further notice.