560I Functional Nutrition - study guide Flashcards
1
Q
How does the early detection of nutrient deficiency prevent chronic degenerative disease?
A
Intervention to restore nutrient levels promotes normal cellular and tissue function.
2
Q
How do standard therapeutic interventions for heart disease or depression affect a patient’s nutritional status?
A
e.g. statins, SSRIs - can exacerbate underlying nutrient insufficiencies or toxic effects
3
Q
As of 2001, how many genetic mutations of PAH were known to cause some variant of PKU? Name the enzyme PAH.
A
More than 400. Phenylalanine hydroxylase.
4
Q
What other enzyme is a principal cause of PKU? How is it involved in the clearance of excess L-phenylalanine?
A
GTP cyclohydrolase. It is involved in the formation of BH4 (tetrahydrobiopterin) which is a required coenzyme for PAH.
5
Q
For enzymes with vitamin-derived cofactor requirements, is there any difference between the clinical outcome from a genetic alteration in the protein structure and dietary deficiency of the nutrient required for production of the cofactor?
A
Lack of enzyme activity will manifest the same. However, differences may arise in the age of onset and severity of outcome (more severe effects are usually only seen with genetic alterations).
6
Q
Why is it unusual to find elevated lipid peroxides when fat-soluble vitamins in serum are in their upper ranges? What other nutrients may therefore need evaluation?
A
Fat soluble vitamins protect against lipid peroxide formation via oxidative stress. May need to evaluate PUFAs, since this scenario may indicate elevated levels of these easily-oxidized FA in membranes.
7
Q
Which vitamin insufficiencies are indicated by elevated branched chain keto acids in urine?
A
B1, B2, B3, B5, lipoic acid
8
Q
How does urinary formiminoglutamate testing add clinical insight to homocysteine testing? What acronym is commonly used for formiminoglutamate?
A
Formiminoglutamate evaluates folate status. Folate deficiency can be ONE cause of elevated homocysteine. FIGLU.
9
Q
Why is ‘folic acid’ deficiency a misnomer? What is the correct term?
A
Folic acid is not an essential nutrient, nor does it generally occur in foods. The correct term is ‘folate deficiency.
10
Q
What is the active form of folate?
A
tetrahydrofolate.
11
Q
Why does direct testing of calcium in serum fail to reveal nutritional status of calcium?
A
Serum calcium is very tightly regulated by PTH (from parathyroid, when Ca++ falls) and calcitonin (from thyroid parafollicular cells, when Ca++ rises).
12
Q
What organ failure most directly causes multiple low trace elements to be found in blood/urine? Why do such patients frequently only show slowly-improving trace element status when supplemented with those minerals only?
A
Stomach - failure of HCl output. Supplementation of trace elements without HCl doesn’t effectively correct the issue. Properly timed pH shifts are required for delivery of elemental salts for absorption in the small intestine.
13
Q
What other nutrient is commonly required as an intermediate ligand for element absorption?
A
Free amino acids and small peptides from dietary protein.
14
Q
What effect does specimen transport have on relative levels of glutamate and glutamine?
A
Gln converts to Glu when specimen analysis is delayed or warmed.
15
Q
What are the competing demands for homocysteine and how can oxidative stress cause imbalance between these pathways?
A
Hcys can be transulfurated to (eventually) form glutathione or methylated to form methionine. Excess oxidative stress can pull hcys into the transfulfuration pathway, leaving less availability for methionine, and subsequent methylation factors like SAMe.
16
Q
What places the greatest demand on absorbed amino acids? Protein synthesis, neurotransmitters or sex hormones?
A
Protein synthesis, by far.
17
Q
What organs have the greatest synthesis rates of proteins?
A
GI tract, liver.
18
Q
What does ADMA stand for?
A
Assymetric dimethylarginine
19
Q
What does ADMA do?
A
Inhibits nitric oxide synthase.
20
Q
What are the effects of excess ADMA?
A
Hypertension due to lack of NO to induce vasodilation.
21
Q
State the reaction of dopamine hydroxylase - its location, substrate, product and cofactors
A
Converts dopamine to norepinephrine in the adrenal medulla and brain. Requires Copper (as Cu++) and vitamin C.
22
Q
How might strongly elevated serine with low glycine on a plasma amino acid profile correlate to poor growth, maldigestion, impaired cognition or excessive fatigue?
A
Normally, gly and ser can be easily interconverted and tend to move up or down together on the profile. If not, the glycine cleavage system may be suspected - possible genetic or toxicant interruption of that system would prevent degradation. Can cause non-ketotic hyperglycinemia. Since the glycine cleavage system is a major source of single carbons for THF pathways, multiple biosynthetic and methylation defects may result.
23
Q
What nutrients are required for the conversion of glycine to serine?
A
B6, Mn, folate
24
Q
How are free-form amino acid products typically customized?
A
Low levels of amino acids in profiles govern amounts added for each. Usual dosing is a rounded teaspoon twice daily.
25
Corrections of what amino acid insufficiencies are found to be helpful in anxiety? Why?
If related to imbalanced brain neurotransmitter function may respond to amino acids that act directly as receptor agonists (Lys, Gly, Tau) or serve as precursors to neurotransmitters (Phe).
26
What amino acid imbalance is indicative of ornithin transcarbamoylase deficiency?
The greatest elevation is usually ornithine (substrate).
27
Into what categories are the fatty acids typically placed on laboratory reports?
Categorized according to chain length within each greater category or desaturation leel or PUFA omega double bond position.
28
What fatty acid is part of the structure of the most active endocannabinoids?
Arachidonic acid
29
What essential fatty acid tends to become persistently low in patients using fish oil supplements?
Arachidonic acid. Superior binding of the n-3 FA to desaturase enzymes tends to suppress the desaturation of linoleic and GLA to form AA.
30
The composition of which lipoprotein is largely revealed in measurements of both serum triglycerides and plasma fatty acids?
Largely LDL particles, since usually done in a fasting state.
31
Which foods are particularly rich in linoleic acid?
(In order of abundance) evening primrose , safflower, grape seed, sunflower and hemp.
32
Which cellular organelle other than mitochondria is required for VLCFA degradation? What clinical consequence is common?
Peroxisomes. VLCFA intermediates cannot be processed in mitochondria, so has to be transported into peroxisomes in order to generate DHA. Thus infants born to women deficient in DHA take a long time to develop their own DHA levels from dietary precursors.
33
What essential nutrient other than PUFAs is required to stimulate peroxisome proliferation?
Simultaneous binding of a PUFA and vitamin A (as 9-cis-retinoic acid) is required to activate PPAR. Deficiency of Vit A or PUFAs may impact fundamental cellular response to energetic or immunological stressors.
34
Would the symptoms associated with linoleic acid deficiency best be described as diverse or specific? Why?
Highly diverse. Central role in 2 processes that broadly impact cellular function: 1. cell membrane properties that affect membrane-bound protein complexes and receptors in all tissues. 2. formation of the dominant eicosanoid precursors, GLA and AA.
35
What fatty acid profile imbalance tends to exaggerate inflammatory responses?
Low levels of n-3 PUFAs (especially EPA) along with elevated AA
36
What essential fatty acid is likely to be found low in patients on aggressive, long-term omega-3 therapy?
Arachidonic acid
37
What clinical syndrome is indicated by finding a 'greater than' sign in the family of saturated fatty acids? i.e. high palmitic and stearic dominating over the family of SFAs. Why?
Metabolic syndrome aka syndrome X, prediabetes, hyperinsulinemia, dysinsulinemia. Insulin stimulates endogenous FA synthesis.
38
Adrenoleukodystrophy is associated with what pattern of fatty acid abnormalities?
Etiology of adrenoleukodystrophy is lack of peroxisome activity required for oxidation and clearance of VLCFA. Those FA accumulate massively, producing chronically progressive neuropathic symptoms.
39
What element cofactor is required by the desaturase enzymes?
Zn++
40
Compare the LCFA profile of borage vs evening primrose oil.
Borage contains GLA only. Evening primrose contains less GLA but is high in LA.
41
```
What fatty acids are recommended for hypertriglyceridemia
Fish oil
Flax Seed oil
Fish and flax
Decrease CHO intake.
```
Fish oil. Decrease CHO intake.
42
```
What primary organic acid abnormalities occur in carnitine deficiency? Elevated?
• Orotate
• Citrate
• Adipate
• Kynurenate
```
Elevated adipate, suberate and ethylmalonate
43
What patterns of abnormalities discriminate mitochondrial inefficiency from ammonia challenge as a cause of citric acid elevation?
Ascribe high levels of citrate, aconitate and isocitrate to ammonia when (a) only citrate, aconitate and isocitrate are found high, or (b) orotate is concurrently elevated.
44
What does NDMA stand for?
N-methyl-D-aspartic acid (a class of ionotropic glutamatergic neuron receptors).
45
Why are NMDA receptors important?
It is those receptors that are agonized by quinolinic acid and potentiated by picolinic acid resulting in potential glutamate toxicity in neurons.
46
What urinary organic acid elevation may justify specifically aggressive vitamin C supplementation?
Elevated p-hydroxyphenyllactic acid (marker for tumor growth) and the concomitant elevated cell division rate stimulation that tends to produce systemic oxidative stress.
47
How does glutathione biosynthesis (from Hcys) relate to the organic acid marker 8-OHdG?
Failure of the reciprocal regulation between transmethylation and transulfuration of Hcys can impair up-regulation of hepatic glutathione synthesis as the major response to oxidative stress, leading to exacerbated and prolonged cellular (esp. mitochondrial) damage from oxidant effects. 8OHdG is a marker of DNA damage due to oxidative stress.
48
Why is supplementation with glucarate salts NOT indicated by abnormalities in urinary glucarate?
Urinary glucarate is a marker for increased hepatic detoxification activity (it is a by-product of pathways leading to glucuronic acid formation). Oral glucarate salts decrease enterohepatic recirculation of carcinogens. See p.365
49
What is the implication of LOW homocysteine for the likelihood of finding elevated alpha-hydroxybutyrate (AHB)?
Elevated AHB indicates up-regulated hepatic glutathione synthesis, and that process demands flow of HCys into L-Cys to form glutathione. Thus low plasma HCys can signal a late-stage of chronic glutathione depletion where total body sulfure amino acid availability is failing to keep up with demand.
50
Explain how elevated benzoate can be a marker of either impaired detoxification or intestinal bacterial overgrowth. What other biomarker can help differentiate the two scenarios?
Elevated benzoate can be due to either (a) failure of hepatic clearance by hippurate formation (impaired detox) or (b) bacterial action on dietary polyphenols releasing benzoate (which exceeds liver clearance capacity). Elevated hippurate indicates scenario (a), low/normal hippurate indicates scenario (b).
51
What is the difference between arabinitol and arabinose? Which one is a urinary biomarker and for what?
Arabinose is a 5-C sugar found in grapes and other fruits/veg. It is a substrate for growth of some bacteria. Arabinitol is the corresponding sugar alcohol that is formed by conversion of dietary CHO by intestinal Candida species. It serves as a biomarker for overgrowth, including severe, invasive cadidiasis.
52
```
Which organic acids are elevated in maple syrup urine disease? Why?
a-ketoisocaproate
a-ketoisovalerate
a-keto-b-methylisovalerate.
all
none
```
Branched-chain keto acids (a-ketoisocaproate, a-ketoisovalerate, and a-keto-b-methylisovalerate. This is due to genetic abnormalities reducing the activity of branched-keto acid dehydrogenase.
53
```
What supplements may assist some forms of maple syrup urine disease? Why do not all forms respond?
Cofactors B1, B2, B3, B5
ALA
Sam-e
Lipoic acid
```
Cofactors B1, B2, B3, B5, lipoic acid may help. But if the SNPs relate to severe alterationsin the enzyme binding sites for the cofactors, supplementation may have no effect.
54
Which organic acids re used to discriminate potential vitamin deficiencies causing homocysteine elevation?
FIGLU (for folate)
MMA (for B12).
AA (for iron)
FIGLU (for folate) and MMA (for B12).
55
Explain how products of the kynurenin pathway can provide evidene of micronutrient status and CNS pertubations.
B6 impairs this pathway - deficiency elevates primarily xanthurenate, but also kynurenic acid/kynurenate. In a B6 sufficient state, Inflammation activates this pathway in the brain leading to products quinolinate and picolinate (since brain does not have enzymes to complete the conversion to nicotinic acid).
56
Explain how glycine insufficiency causes elevated pyroglutamate?
Glycine is required in the kidney to sustain reformation of glutathione. Lack of glycine is one reason why the critical gamma-glytamyl pathway is truncated prior to executing the GSH reconstruction, causing release of the glutamic acid moiety as pyroglutamate.
57
Why might an interruption in the TCA cycle at any single step NOT always cause low level of products and high levels of preceeding substrates?
The mitochondrial membrane is selectively permeable, regulated by transport proteins. Thus specific TCA cycle intermediates can easily leave and their levels do not become elevated.
58
How can smoking be connected to glucarate levels?
Smoking can increase urinary glucarate levels, indicating activity of hepatic detoxification.
59
What does a 6-month progressive lowering of urinary sulfate with persistent elevation of pyroglutamate imply about a patients' prognosis? What specific nutrient interventions are indicated?
Progressively lowering sulfate indicates chronic toxicant challenge/oxidative stress. Pyroglutamate elevation indicates that glutathione losses may be a contributing factor. Glutathione support is indicated via GSH or precursors (Cys, Met, Gly, and related amino acids. Tau, Ser, Thr may be helpful in restring GSH status.
60
What three peptides make up glutathione?
Cys - Gly - Glu
Cys - Lys - Glu
Phe - Gly - Lys
Cys - Gly - Glu
61
What is a metabolic rationale for the high incidence of hypochlorhydria?
Decline in stomach acid output with age, likely associated with underlying metabolic changes tied to nutrient insufficiencies and toxic effects.
62
What nutrient insufficiencies can lead to impaired HCl output in the stomach?
Zinc, biotin (for protein synthesis suport), B complex, iron, CoQ10 for mitochondrial activity.
63
What nutrient insufficiencies are generally caused by low HCl?
Protein and major/trace elements.
64
What patterns of abnormalities in stool chemistries are found in conditions of low stomach acid?
Abnormal commensal bacterial distributions.
65
What patterns of abnormalities in stool chemistries are found in conditions of low pancreatic enzymes?
Decreased digestion of dietary components (esp protein) resulting instimulation of certain bacteria that metabolize amino acids.
66
What patterns of abnormalities in stool chemistries are found in conditions of impaired small bowel absorption?
Decreased absorption of dietary components stimulates microbe growth due to availability of growth substrate.
67
What are the different clinical values of testing for leaky gut with the lactulose-mannitol challenge and IgG4 testing?
Lactulose-mannitol (lactulose is normally poorly-absorbed, mannitols is normally well-absorbed) evaluates intestinal permeability. However, it does not also answer the question about whether macromolecules from food are regularly permeating the intestinal barrier and producing immunological responses - serum IgG4 would do that.
68
How does complement cascade activation explain differences between clinical interpretations of elevated serum IgG1 and IgG4 class antibodies to food antigens?
IgG1 class antibodies are those that are first produced in reaction to food components penetrating intestinal barriers. IgG1-food complexes are degraded by complement systems. However, complement proteins do not recognize IgG4-food complexes, so they remain in circulation much longer (days to weeks).
69
What intestinal bacterial genus is suspected to be prevalent in the patient with high p-hydroxyphenylacetate, 8-OHdG, orotate and glucarate?
Ammonuria indicated by elevated orotate suggests the bacteria genera capable of high ammonia production, including clostridia, enterobacter and Bacillus.
70
Below the threshold dose, how do responses predicted by the hormesis model differ from those derived from the threshold model?
Threshold models presume nil response below the threshold for positive responses. Hormesis models predicts (or allows) negative responses in the regions below the threshold for positive responses.
71
How might the hormesis model explain lower incidence of breast cancer in women who smoke tobacco?
Smoking below the threshold for increasing cancer incidence might produce lower risk via mechanisms such as induction of hepatic detoxification systems that lower total body estrogen exposure.
72
Why does oral DMSA cause dramatic increases in urinary elemental levels in patients with high body burdens of toxic elements?
When a patient with a high body burden of a toxic element starts DMSA therapy, loses on a given day may be offset by release of the element from deep stores such as bone over a time interval longer than the urine collection during therapy. The DMSA can act to stimulate mobilization of old pools with slow turnover.
73
What compound reacts with acetaminophen to initiate mercaptan formation?
Glutathione. This explains the potential for uncontrolled oxidative stress and organ failure due to overdosing of drugs like acetaminophen that produce high demand for hepatic glutathione conjugation.
74
What is your interpretation of an elevated plasma Cys/Sulfate ratio and low urinary sulfate, together with high urinary mercury, and high 8OHdG?
Lack of sulfur compound precursors is hampering sulfoxidation and probably impairing maintainance of glutathione reserves. Causative factor is most likely mercury, which is causing DNA damage.
75
What micronutrient is specifically likely to assist the patient with elevated benzoate
Glycine for glycine conjugation (phase II reaction). The reaction also requires Coenzyme A, so high rates of reaction can drain pantothenic acid reserves. So pantothenate would also help.
76
Why does mercury toxicity produce elevations of precoproporphyrin, pentacarboxyporphyrin and coproporphyrin (total)?
Urophorphyrin decarboxylase catalyzes a series of 4 decarboxylation reactions. After each step the product must dissociate from the enzyme and re-associate in a new confirmation that places the next carboxyl group at the active site. Mercury binds strongly to the enzyme such that the product of the third decarboxylation (pentacarboxyporphyrinogen) has difficulty reentering the site, causing it to accumulate and spill into urine. The prior step also backs up, causing hexacarboxyporphyrinogen to spill also. Meanwhile, the excess pentacarboxyporphyrinogen is converted to precoproporphyrin.
77
What are common symptoms of a pathological detoxifier? What specific observation indicates phase II detox difficulty from these options: elevated bilirubin, or high caffeine clearance?
Symptom-free until biotransformation systems are stressed; then noticeable symptoms appear. Elevated bilirubin indicates difficulty with glucuronidation.
78
Why is excess phase I activity with relative phase II deficiency a cause for concern?
Phase I products tend to become even more toxic than their precursors.
79
What trace elements are involved in protecting against oxidative stress?
Zinc and copper in superoxide dismutase (cytosolic). Manganese in superoxide dismutase (mitochondrial). Selenium in glutathione peroxidase.
None
All
Zinc and copper in superoxide dismutase (cytosolic). Manganese in superoxide dismutase (mitochondrial). Selenium in glutathione peroxidase.
80
```
What micronutrients are needed for the regeneration of GSH?
Selenium
B2 (as FAD)
B2
B3 ( as NADPH)
B3
```
Selenium, B2 (as FAD) and B3 (as NADPH).
81
What is the role of vitamins A, C, E and beta-carotene in oxy-stress?
Removing oxygen radicals.
82
Why should botanical sources of antioxidants, such as Panax ginseng or Ginkgo biloba, be considered rather than individual antioxidant micronutrient supplementation?
Because balanced intake of all of the antioxidants is superior to individual supplementation because of the demonstrated codependence.
83
What factor released during sleep adds strong protection against oxidative stress?
Melatonin. It's roughly twice as effective as vitamin E for protection against the peroxyl radical.
84
Why is it unusual to find elevated levels of lipid peroxides when fat-soluble nutrients are in their upper ranges? What other nutrients might therefore need evaluation?
Good levels of fat-soluble vitamins should indicate protection against oxidative stress especially in cell membranes, where oxidative stress without adequate protection would lead to elevated lipid peroxides. It would be important to evaluate membrane FA components, since it may be that levels of easily-oxidized PUFAs are elevated.
85
Consider the similarities between hormones and microRNAs.
Did you consider them? Basically, just understand that the body uses a full and diverse array of cell regulators to achieve homeostasis in spite of dramatic fluctuations in daily habits and circumstances.
86
What is the danger of therapeutic use of hormones?
There is a danger of overuse because they are part of a delicate balancing system.
87
What are the effects of excess growth hormone?
Gigantism, acromegaly, other malformations.
88
What are the effects of deficient growth hormone?
Depends on age. In young children - growth failure. In adults - metabolic syndrome, osteoporosis, muscle wasting, impaired quality of life, increased cardiovascular events.
89
What are the effects of excess thyroxine?
Palpitations, heat intolerance, nervousness, insomnia, breathlessness, increased bowel movements, light/absent menstrual periods, fatigue, fast heart rate, trembling hands, weight loss, muscle weakness, warm/moist skin, hair loss, staring gaze.
90
What are the effects of deficient thyroxine?
Fatigue, weakness, weight gain, hair loss, cold intolerance, muscle cramps, constipation, depression, irritability, memory loss, abnormal menstruation, decreased libido, pale/dry skin, coarse/dry hair, puffy face, hoarse voice, elevated blood cholesterol.
91
What are the indications of excess DHEA?
May be an early indicator of depression.
92
What are the effects of deficient DHEA?
Low levels of sex hormones testosterone and estrogen. DHEA also has immune-modulating effects and prevents stress-induced damage to the hippocampus, as in Alzheimer's Disease.
93
What are the effects of excess cortisol?
Blocks insulin action (so increased blood sugar), suppresses immune system, increased protein breakdown. May cause greater urinary losses of B-vitamins, lowered mineral status and reuced absorption of calcium, and a greater need for vitamins C and E.
94
What condition is associated with low cortisol?
Cushing's syndrome
Hoshimotos'
Addison's
Adrenal insufficiency, showing lowest cortisol in morning.
Adrenal insufficiency, showing lowest cortisol in morning.
95
What condition is associated with excess cortisol output, especially in the evening, when cortisol should be naturally falling?
Cushing's syndrome
Hoshimotos'
Addison's
Adrenal insufficiency, showing lowest cortisol in morning.
Cushing's syndrome.
96
How is sIgA linked with chronic stress?
Decreased sIgA in chronic stress.
Increased sIgA in chronic stress.
Decreased sIgA in chronic stress.
97
What are the possible effects of elevated estradiol.
May simulate immune response. Increased breast cancer risk. Increased prostate cancer growth. SYmptoms include anxiety, difficulty sleeping, irritability. Breast fibroids or cysts.
98
What are the possible effects of deficient estrogen?
Breast cells will not mature properly. Menopausal symptoms.
99
Increased free estrogen (via increased sulfatase activity), urinary incontinence, decreased coordination, slowed reflexes, impaired memory and reasoning skills, increased risk for diabetes. Possibly migraines. Possibly chronic fatigue are the possible effects of excess _____
progesterone
100
```
What vitamin has been shown to increase levels of progesterone?
Vitamin A
Vitamin C
Vitamin D
Vitamin E
```
Vitamin C
101
What are the effects of low testosterone?
High cortisol, possibly metabolic syndrome, T2DM and cardiovascular disease.
102
What are the effects of high testosterone
Increased risk for growth of prostate cancer cells.
103
What advantage may be derived from the use of a patient's genomic data when choosing drug therapies?
• Specific SNPs can be corrected by proper drug selection.
• Dosages may be adjusted according to SNPs that effect their metabolism.
• Drugs can be targeted to change gene expression.
• Patients with certain genomic features are referred for naturopathic care.
• Dosages may be adjusted according to SNPs that affect their metabolism
Drugs are metabolized/cleared via detoxification enzymes. Thus SNPs in phase I CYP enzymes or phase II enzymes may alter the patient's clearance rates of that drug.
104
What information does the term C677T convey about a SNP?
Specifies location (base number 677) and nucleotide replacement (cytosine to thymine) that is present.
105
What proportion of drugs are metabolized by the cytochromes uniquely required for forming 16a-hydroxyesterone?
The CYP3A4 and CYP2E variants required for 16a-hydroxyestrone formation are present at 35% and 4% respectively.
106
What steps in the overall process from DNA expression to cellular outcome are potentially impacted by environmental factors?
All steps including DNA transcription, RNA translation and protein function are potentially impacted by environmental factors.
107
What types of biochemical lesions are involved in the etiology of chronic diseases?
Amino acid substitutions/deletions in protein primary structures that can affect structure and function.
Toxicants may also change cell structural components or may block enzyme active sites.
