CAM411A Advanced Nutrition Medicine: Fortnightly Discussion Responses

This document presents a collection of nutrition discussion responses covering various topics including the role of folate in cancer, the effects of vitamins A, D, E, and K on the immune system, nutritional interventions for mitochondrial dysfunction in neurological disorders, the role of carnitine in cardiomyopathy, and the impact of ketogenic diets and fasting on cancer cells. Each section provides evidence-based insights and references to support the claims, addressing complex biochemical mechanisms and therapeutic applications in nutritional medicine. The discussions highlight the controversies and complexities in nutritional research, emphasizing the need for further investigation and personalized approaches to dietary interventions. Desklib provides a platform to access such comprehensive assignments and past papers for students.

Running head: NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Name of the Student:
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1NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Weeks 1-2
Current evidence based literature demonstrates conflicting findings with regards to the
contribution of the water solution, vitamin B9 or Folate, in the emergence and promotion of
cancer within the body. One of the major functions of folate is to facilitate the metabolism of one
carbon components, for the purpose of synthesizing nucleotides and progression of methylation
reactions (Chittiboyina et al., 2018). 5-Methyltetrahydrofolate (5-MTHF), also known as
methylated folate, in combination with cobalamin, are essential for the conversion of methionine
from homocysteine, which is further converted to S-adenosylmethionine (SAM). SAM
contributes to DNA and RNA methylation and thus, its deficiency has been linked to inadequate-
methylation-induced disruption in gene transcription, alteration in genetic expression of tumour
genes which further facilitates proto-oncogene formation. However, an excess intake of folic
acid has also been linked to cancer promotion (Cheung et al., 2016). Folic acid is converted to
the active form, tetrahydrofolate via dihydrofolate reductase (DHFR) enzyme. An excess intake
of approximately 400 mcg of folic acid has been evidenced to cause saturation of the DHFR
enzyme which in turn can pave the way for excessive inactive folic acid which in turn,
demonstrates positive associations with cancer progression. To approach this controversy in
current clinical practice, there is a need to implement further evidence based research since
current studies are greatly heterogenous in nature, which each trial evidencing folate associations
with cancer at various cutoffs and standards (Catala et al., 2019). Additionally, it is worthwhile
to note that cancer metabolism is linked with a range of nutritional and enzymatic factors other
than folate, and may even vary with respect to ethnicities, dietary patterns and lifestyle. Thus,
there is a need for more evidence based research inclusive of dietary and enzymatic variations

2NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
rather than merely focusing on folate, in order to arrive at a clinical consensus (Young Park et
al., 2018).
References
Catala, G. N., Bestwick, C. S., Russell, W. R., Tortora, K., Giovannelli, L., Moyer, M. P., ... &
Duthie, S. J. (2019). Folate, genomic stability and colon cancer: The use of single cell gel
electrophoresis in assessing the impact of folate in vitro, in vivo and in human
biomonitoring. Mutation Research/Genetic Toxicology and Environmental
Mutagenesis, 843, 73-80.
Cheung, A., Bax, H. J., Josephs, D. H., Ilieva, K. M., Pellizzari, G., Opzoomer, J., ... & Canevari,
S. (2016). Targeting folate receptor alpha for cancer treatment. Oncotarget, 7(32), 52553.
Chittiboyina, S., Chen, Z., Chiorean, E. G., Kamendulis, L. M., & Hocevar, B. A. (2018). The
role of the folate pathway in pancreatic cancer risk. PloS one, 13(2).
Young Park, J., Bueno-de-Mesquita, H. B., Ferrari, P., & Bradbury, K. E. (2018). Dietary folate
intake and pancreatic cancer risk: Results from the European prospective investigation
into cancer and nutrition. International Journal of Cancer, 144(7).

3NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Weeks 3-4
Vitamin A has been evidenced to yield diverse and rather disparate effects on the immune
system of the body. Retinoic acid (RA), a metabolite of vitamin A, has been evidenced to
facilitate T-cell production, which in turn has the potential to reduce immune function in
response to body’s as well as foreign antigens, including the ones produced by the gut
microflora. Paradoxically, deficiency of vitamin A has been evidenced to hamper vaccination
response as well as enhance the risk of acquiring pulmonary and gastrointestinal infections
(Erkelens & Mebius, 2017). Vitamin D on the other hand has been evidenced to stimulate the
production of a substance CD31 by dendritic cells, which in turn has the ability to reduce T cell
activation - a key precursor of autoimmune diseases. Additionally, Vitamin D has also been
evidenced to reduce the proliferation of B and T cell proliferation and differentiation as well as
facilitation of T regulatory cell induction. These processes have been evidenced to increase anti-
inflammatory cytokine and decrease pro-inflammatory cytokine production (Dimitrov & White,
2016). The supplementation of Vitamin E on the other hand, has been evidenced to enhance
positive selection by the epithelial cells of the thymus resulting in increased differentiation of
immature T cells, which in turn improves cellular immunological functions (Wu & Meydani,
2017). Menaquinone-4, a form of Vitamin K has been evidenced to reduce the mRNA and
protein expression of proto-oncogene cyclin D1 – a key stimulation of pro-inflammatory ad
carcinogenic NF-KB signaling, thus resulting in enhance anti-inflammatory and immunological
functioning. From the above mechanisms it can be observed that while Vitamins A, D and E
demonstrate similarities in terms of T cell regulated immunity enhancement, Vitamin K adopts
an anti-inflammatory approach to immunity stimulation. Additionally, despite T cell regulation

4NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
mechanisms, Vitamins A and E target cellular and innate immunity whereas Vitamin D regulates
autoimmune functioning (Namazi, Larijani & Azadbakht, 2019).

5NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
References
Dimitrov, V., & White, J. H. (2016). Species-specific regulation of innate immunity by vitamin
D signaling. The Journal of steroid biochemistry and molecular biology, 164, 246-253.
Erkelens, M. N., & Mebius, R. E. (2017). Retinoic acid and immune homeostasis: a balancing
act. Trends in immunology, 38(3), 168-180.
Namazi, N., Larijani, B., & Azadbakht, L. (2019). Vitamin K and the Immune System.
In Nutrition and Immunity (pp. 75-79). Springer, Cham.
Wu, D., & Meydani, S. N. (2017). Vitamin E, Immunity, and Infection. In Nutrition, Immunity,
and Infection (pp. 197-212). CRC Press.

6NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Weeks 5-6
A number nutrient intake mechanisms and nutritional interventions have been evidenced
to mitigate mitochondrial dysfunction and in turn, the progression neurological disorders.
Aberrant forms of mitochondria as well as abnormalities or deficits in the functioning of
mitochondria located at dopaminergic neurological sites have been evidenced to be loosely
associated with neurological disorders like Parkinson’s disease (McClave et al., 2019).
Deficiencies in Complex 1 of mitochondria driven oxidative phosphorylation has been evidenced
to facilitate inflammatory reactive oxygen production – a key precursor Parkinson’s. Nutritional
interventions like a ketogenic diet have been evidenced to mitigate the same by stimulation of
beta oxidation of lipids which in turn, facilitates electron transport from Complex I to II and
hence, correction of Complex I deficiencies (Zweers et al., 2018). Ketogenic diets have also been
evidenced to corrected mitochondrial dysfunction induced Parkinson’s via ketone body-induced
reduction of oxidative stress which in turn, enhances cerebral ATP production and metabolism of
glucose. Additionally, restriction in dietary intake of methionine has been evidenced to reduce
reactive oxidative species production in complex 1 and thus, mitigation of mitochondrial
dysfunction in neurological dysfunction (Nichols, 2018).

7NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
References
McClave, S. A., Wischmeyer, P. E., Miller, K. R., & van Zanten, A. R. (2019). Mitochondrial
Dysfunction in Critical Illness: Implications for Nutritional Therapy. Current nutrition
reports, 8(4), 363-373.
Nichols, T. W. (2018). Mitochondrial dysfunction in our aging veterans; obesity, fatty liver, and
NASH with obstructive sleep apnea treated with CPAP, medication, nutrition and MOVE
program. Sleep Med Dis Int J, 2(2), 45-49.
Zweers, H., Janssen, M. C., Leij, S., & Wanten, G. (2018). Patients with mitochondrial disease
have an inadequate nutritional intake. Journal of Parenteral and Enteral Nutrition, 42(3),
581-586.

8NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Weeks 7-8
Low levels of carnitine can be found in cardiomyopathy patients due to an autosomal
recessive disorder known as primary carnitine deficiency, which in turn, impairs the oxidation of
fatty acids. This is caused due as a result of the carnitine transporter OCTN2. A key mechanism
of action demonstrated by L carnitine in the oxidation of fatty acid is its role of being carrier of
long chain fatty acids from cytoplasm to mitochondria, which in turn, facilitates long chain fatty
acid beta oxidation to form of carbon dioxide and energy (Bursle et al., 2017). These can then be
used by muscles in the myocardium which explain the reason behind carnitine deficiency and
cardiomyopathy. Supplementation of 500 to 200 mg/day has been evidenced to demonstrate
benefits like: improved lipid metabolism, reduced oxidative stress and blood pressure, enhance
muscle oxygen supply for improved athletic performance and regulation of diabetic symptoms of
hyperglycemia via enhanced 5' AMP-activated protein kinase production (Lahrouchi et al.,
2017).

9NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
References
Bursle, C., Weintraub, R., Ward, C., Justo, R., Cardinal, J., & Coman, D. (2017). Mitochondrial
Trifunctional Protein Deficiency: Severe Cardiomyopathy and Cardiac Transplantation.
In JIMD Reports, Volume 40 (pp. 91-95). Springer, Berlin, Heidelberg.
Lahrouchi, N., Lodder, E. M., Mansouri, M., Tadros, R., Zniber, L., Adadi, N., ... & Ratbi, I.
(2017). Exome sequencing identifies primary carnitine deficiency in a family with
cardiomyopathy and sudden death. European Journal of Human Genetics, 25(6), 783-
787.

10NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
Weeks 9-10
Ketogenic diets have been evidenced to enhance the oxidative stress of cancer cells by
enhanced lipid metabolism which in turn will limit the availability of glucose required for
glucose-6 phosphate pyruvate generation – components responsible for reduction of
inflammatory hydroperoxides. Further, high lipid metabolism due to ketogenic diets compels
cancer cells to derive energy from mitochondria (Branco et al., 2016). Mitochondria are already
dysfunctional in cancer cells paving the way for reduction of oxygen to singlet oxygen and
exposure of cancer cells to reactive oxygen species and oxidative stress. Similarly, fasting and
intermittent fasting interventions for short periods of 48 hours have been evidenced to induce
cardioprotective and immunity-enhancing functions via reduced insulin production. However,
such protective effect are not responded to by abnormal cancer cells thus rendering them
susceptible to chemotherapeutic action – a process known as differential stress resistance
(Valenzano et al., 2019).

11NUTRITION DISCUSSION FORTNIGHTLY RESPONSES
References
Branco, A. F., Ferreira, A., Simões, R. F., Magalhães‐Novais, S., Zehowski, C., Cope, E., ... &
Cunha‐Oliveira, T. (2016). Ketogenic diets: from cancer to mitochondrial diseases and
beyond. European journal of clinical investigation, 46(3), 285-298.
Valenzano, A., Polito, R., Trimigno, V., Di Palma, A., Moscatelli, F., Corso, G., ... & Astuto, M.
(2019). Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral
Adipose Tissue, and ROS Production. Antioxidants, 8(12), 643.