Here in this fourth and final part of this (work-in-progress) Self Meta ~ we are arriving gently to a concluding discussion spanning throughout the following cliff-notes and expectations moving forward:

The need to advance further dialogues and self-research beyond the confines of this Self-Meta.
As strictly an N=1 hypothesis under this author’s (AW) own microcosm ~ 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 (~ as per external liaison, diagnosis and advisory through functional medicine) to assess and/or diagnose, if any ~ disorders anywhere throughout the inactive > active Vitamin D metabolism pathway.
Subsequently, the need to consider any other profiling tests that may be of relevance and/or affecting the Vitamin D metabolism. Namely:
- Vitamin D nutrigenomics / including metabolism, and storage pathways.
- Vitamin B / methylation pathways.

1st July 2022 ~ Strictly WIP / work in progress.

Discussion

The opposition to Vitamin D supplementation remains both justified and warrants attentive individualisation. Especially those who are affected or inherited with auto-immunity or genetic dysfunctions of Vitamin D may find the opposition side (Marshall, T. 2018) noteworthy and compelling. However, other topics worth mentioning, albeit lengthy to be included here for accessible reading ~ are the numerous confounding factors impacting hyper-absorptions. To name a few ~ Vitamin A, K2, magnesium status, and interestingly ~ dietary calcium.

Purely from global / institutional perspective, 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).

Nuances 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:

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.

What to look for and sought ~ Course of Actions with a practitioner.

First and foremost this Self-Meta is contemplative and certainly not prescriptive in any way it exerts confidence that the following may (or may not) be readily applicable to reader’s circumstance, both sociological and financial.

The very first pragmatic course of action would obligate a search and research ~ of the nearest nutrigenomics profiling. However even before doing so, readers should be well aware of the following pre-requisite(s) prior any consultation and/or proceedings tot ake place:

Cost & accessibility. Nutrigenomics is a highly sought after alternative wellness; often consequenting 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.
Nuanced responsibility(s) for extrapolating 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. Such a package to feature anyway from at least four (4) all the way to thirteen (13) or more reports detailing genomic interpretaitons based off the collected DNA data.
3. Each of the above report provides a biochemistry overview and implications on wider health and surrogate markers beyond a summary of polymorphisms results.

As one expects, there bounds to be a significant investment towards 1) financial investment and 2) ~ knowledge willingness for readers to take with them not merely days as cross sectional insight. But likely years to compel and prompt insight, self-intervention opportunities or ~ the need to sought second or third consultation for deeper investigations. Regardless, critical reading and maintaining an open dialogue remains key in all proceedings amidst alternative health and wellness consulting.

Due to the limited spacing of this Self Meta this Author (AW) may soon be obliged to produce an insight feature presentation to enlighten all of the above and more ~ in multiple uploads.

What genes should I test? A mini section on Nutrigenomics

This section is likely reserved for an extended writing, however a few grossly-summarised / preliminary thoughts on specific genes are shared here that are deemed essential at managing various realms of Vitamin D handling. Depending on reader’s curious nuance these genes may be highly generalised or specifically tied to certain realm of functions. To name a few ~ activation / conversion, inactivation, excretion, mobilisation (to target tissue), reception/receivals, governance /self-adjustment mechanisms. Below is a hypothetical listing, though certainly not exhaustively complete at addressing these responsibilities (Hu, Z et al. 2019), (Tomei S. et al. 2020) and (Malloy PJ and Feldman D 2011).

7-dehydrocholesterol reductase / NAD synthesise 1 (DHCR7/NADSYN1).
Notable role and/or function(s): Conversion ~ in the early pathway (Skin)
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)
Cytochrome P450 Family 24 Subfamily A member 1 (CYP24A1).
Notable role and/or function(s): Self-adjust / control mechanism at preventing toxicity symptoms.
1-Alpha-hydroxylase (CYP27B1)
Notable role and/or function(s): Conversion ~ in the intermediary pathway (25OHD into active 1,25 OHD).
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.
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.

Other co-morobidities yet to be included in this Self-Meta.

Obviously this Self-Meta is not able to contain other nuances in favour of accessible reading. 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):

Related minerals handling / metabolism disorders ~ particularly:
1. calcium,
2. magnesium,
3. phosphate.*
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> —

Pragmatism / Personal Course of Action / Synthesis.

In light of the literatures presented in this Self-Meta This Author (AW) would like to present his own course of action, under personal nuanced circumstance. Chiefly having considered the literatures he hereby:

Maintains view that Vitamin D; be it however deriving from food and/or sunlight source – remains an inseparable part in life ecosystem.
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.
Maintains a need to periodically set aside finance(s) for the nutrigenomics tests as outlined earlier in this final part of Self-Meta.
Maintains self-journalling, interest, research and enquiring on themes of nutritional science, and maintain question(s) by however ways respect upon the presently established consensus.

Vitamin D, whether exogenously through nutrition or that of sunlight source – both remain necessary for physiological, and psychological homeostasis. “Stasis” here as This Author asserts ~ remains open to individual interpretation and thus in and of itself does not suggest a linear confidence on another’s complex and often nuanced and thereby “individual” ~ circumstance.

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.

In light of the above, pragmatism nonetheless seemingly points towards acquiring the need for emphatic Nutrigenomics profiling. Disadvantages to these of course remains immediate such that they are often costly, inaccessible to the general public, and certainly requiring more disciplined willingness, and responsibility to read all nuances of nutritional science; much more than a pedestrian knowledge.

It is safe to say thus, when extrapolating a course of action with a third party ~ General Practitioners ~ sadly ~ with all due respect sadly does not suffice as be-all and end-all point of care. Medical paternalism remain sadly unaddressed in modern medicine practice; thereby prohibiting patient’s scientific enquiring.

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.

However if there is one thing we can safely take away as an immediately accessible closing perspective here is the question of pragmatism / practicality. 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).

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.

The above course of action could be grossly summarised as periodical cycling of dosages between none low and high as accordingly to seasons. Much lower during summer (to encourage and leverage sun exposure) but higher during winters.

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.

(Self-Meta) Vitamin D ~ For and Against (Part 4 of 4)