**9. Conclusion**

In summary, in the current literature, several lines of evidence suggest a tight link between vitamin D3 and neurodegenerative diseases (see **Table 1**). Besides epidemiological studies, vitamin D deficiency influences several pathways associated with neurodegenerative diseases, which also indicates a causal link of hypovitaminosis D and AD, MS, and PD. As a consequence, vitamin D hypovitaminosis is broadly assumed to be a risk factor for these diseases. In addition, recent literature underlines a potential link between prion diseases, ALS, HD, and neuropsychiatric

**137**

**Alzheimer's disease**

> Epidemiological and clinical studies

Vit. D levels ↓

Vit. D levels ↓

Risk factor [96, 103] Genetic predisposition [99–101] Causal link [109–111]

/

> [76–79] Severity of PD [80–81, 83] Genetic link

[85–86]

Animal and cell

Causal link

Causal relationship

Regulatory

Vit. D2 as suitable

Potential role of the

Vit. D supplementation ↓

prolonged lifespan

[149]

Epigenomic action on *HTT*

therapeutic candidate

VDR

[138]

Benefits after

supplementation

gene

[150]

[139, 140]

Inflammation [141]

Potential transcriptional

regulation of *HTT* gene

[150]

Ca2+ homeostasis

[142]

[128]

T cells ↑

[112]

[63]

[63]

Transcription

[62]

Molecular

APP homeostasis

Dopamine

Immunomodulatory effects

Reduced

oligomerization of

prions

[128]

homeostasis

[113]

Ca2+ homeostasis [114]

[64–69]

Neurotrophins

[89]

Antioxidative

properties

[91]

Ca2+ homeostasis

[71–73]

Inflammation

[74]

Ca2+ homeostasis

[6]

Intervention studies

Beneficial

Beneficial in

Beneficial

/

Variable outcomes

/

[131, 134]

[115–118]

Vit. D as genetic and

environmental risk factor

[124]

dependence of

genotype

[87]

*Vit. D, vitamin D; APP, amyloid precursor protein; Ca2+, calcium; PD, Parkinson's disease; VDR, vitamin D receptor;* ↓ *reduced.*

*Summary of the current research findings about the influence of vitamin D on selected neurodegenerative diseases Alzheimer's disease, Parkinson's disease, multiple sclerosis, prion disease,* 

*amyotrophic lateral sclerosis, and Huntington's disease in respect to epidemiological and clinical, animal and cell culture studies, identified molecular mechanisms, and intervention studies.*

**Table 1.**

[58]

[92]

mechanisms

culture studies

[39, 40] Risk factor [41, 43–48] Causal link [51–56]

**Parkinson's disease**

**Multiple sclerosis**

**Prion disease**

**Amyotrophic lateral sclerosis**

**Huntington's disease**

Non-consistent

Vit. D levels ↓ [148]

findings

[132, 133, 136]

Evidence of genetic

link

[137]

*The Effects of Vitamin D Deficiency on Neurodegenerative Diseases*

*DOI: http://dx.doi.org/10.5772/intechopen.89160*


*Summary of the current research findings about the influence of vitamin D on selected neurodegenerative diseases Alzheimer's disease, Parkinson's disease, multiple sclerosis, prion disease,* 

*amyotrophic lateral sclerosis, and Huntington's disease in respect to epidemiological and clinical, animal and cell culture studies, identified molecular mechanisms, and intervention studies.*

*The Effects of Vitamin D Deficiency on Neurodegenerative Diseases DOI: http://dx.doi.org/10.5772/intechopen.89160*

*Vitamin D Deficiency*

disorders.

A potential link between vitamin D3 and depression is subject of current research, and for more detailed information about the potential role of vitamin D on major depressive disorder, we recommend a review from Casseb et al. [163]. A meta-analysis from Parker and colleagues concluded that there are increasing evidences for an influence of vitamin D on depression [164], and in line with this, another review also postulated hypovitaminosis D as risk factor for late-life depression [165]. Consistently, a very recent meta-analysis reported a negative association

A following cross-sectional study including 100 women in reproductive age also shows that the depression score inverse correlated with the vitamin D serum level [167]. Contradictorily, a supplementation with 1200 IU vitamin D for 12 months failed to have an influence on the prevention of depression in a very recent, randomized clinical trial including 155 participants having clinically relevant depressive symptoms [168]. Furthermore, a recent MR study from Libuda and colleagues indicates no causal relationship between both depressive symptoms and broad depression and vitamin D levels due to a missing association of six vitamin D-related SNPs with depression [169]. In summary, the current research investigating the role of vitamin D3 in depression is much less clear than other neurological

In respect to the chronic mental illness schizophrenia, it could be shown that hypovitaminosis D is common in patients [170]. This fits to the environmental risk factors that have been described for schizophrenia, like season of birth [171] and latitude [172]. Also a link between neonatal vitamin D levels and the schizophrenia risk was reported [173]. A recent randomized, placebo-controlled study from Krivoy and colleagues examined psychosis severity, mood, cognition, and metabolic profile in 47 schizophrenia patients during an 8-week supplementation of 14,000 IU vitamin D/week. The authors described no significant effects on psychosis, mood, or metabolic status, but a trend to an improved cognitive function accompanied by significant elevated vitamin D levels in the supplemented group. A possible explanation for these findings, given by the authors, could be that a medical score that measures the symptom severity in schizophrenia patients decreased during the study in the placebo as well as in the treated group and could thereby veil the influence of supplemented vitamin D [174]. An actual study reported beneficial effects of supplementation of vitamin D3 in combination with probiotics in schizophrenia patients [175]. Addressing the underlying molecular mechanism, vitamin D could perform its suggested beneficial actions via modulation of immune system and inflammation processes since it was reported that patients with chronic schizophrenia have significantly elevated levels of TNF-α and IL-6 [176]. Furthermore, it could be shown that the expression of genes involved in the metabolism of vitamin D3 (*VDR*, *CYP27B1*, *CYP24A1)* is significantly elevated in peripheral blood of schizophrenic patients [177], indicating a potential causal relationship between vitamin D3 and schizophrenia, which should be the aim of future research.

In summary, in the current literature, several lines of evidence suggest a tight link between vitamin D3 and neurodegenerative diseases (see **Table 1**). Besides epidemiological studies, vitamin D deficiency influences several pathways associated with neurodegenerative diseases, which also indicates a causal link of hypovitaminosis D and AD, MS, and PD. As a consequence, vitamin D hypovitaminosis is broadly assumed to be a risk factor for these diseases. In addition, recent literature underlines a potential link between prion diseases, ALS, HD, and neuropsychiatric

of serum 25(OH)D3 levels with the risk of depression [166].

**136**

**9. Conclusion**

diseases and reduced Vitamin D level; however, it has to be emphasized that many aspects of vitamin D remain obscure in these diseases. Therefore, further studies to clarify and judge a potential beneficial effect of vitamin D3 are needed to unravel the exact role of vitamin D in brain metabolism and neurodegenerative diseases. Especially determination of the individual serum 25(OH)D3 levels by appropriate methods like mass spectrometry and taking the individual patient's competence to metabolize or form active vitamin D3 into consideration will help to avoid ambiguous results. The fact that several prospective studies investigate a mixture of several different nutritional components makes it hard to trace the observed effects back to vitamin D in particular at the moment.

Interestingly some European countries, like Finland, already supplement vitamin D in general in food to prevent hypovitaminosis in the elderly population, and an optimal intake of 2000–4000 IU vitamin D or 10–20 min sunlight exposure per day is already recommended by experts, for example, at the Joint International Symposium Vitamin D in Prevention and Therapy and Biologic Effects of Light (2019). Further studies will help to validate the beneficial effects of these recommendations.
