CAR Nutritional Considerations

Abstract
This review includes a seven point nutritional summary:
1) 2 lbs nutritious vegetables for C, B2, Folate, A, E, K, Calcium, Potassium, and N-3 18:3 alpha linolenic essential fatty acid (EFA).
2) Marginal vegetables such as beans and tubers may present excessive viscous fiber including pectin - having a broadening effect on the small intestinal villi reducing their number and absorptive surface. Medium chain sugars may increase flatulence and glycoalkaloids in potatoes cause body odor.
3) 3-7 oz meat/fish/poultry provides protein, B-12, iron absorption enhancement, and supports skeletal muscle carnitine transport capacity. Pork and poultry are low in B-12.
4) Whole wheat has high fiber and digestion resistant starch (RS) - too much bulk if consumed to meet all calorie needs. About 1% of the population may be wheat intolerant expressed as celiac disease.
5) Oats have a high proportion of rapidly fermenting viscous fiber - insufficient bulk and fermentation to the distal portion of the large intestine.
6) Brown rice has optimal fiber - nutrients include magnesium, phosphorous, iron, zinc, selenium, B-1, niacin, B-6, pantothenic acid, and N-6 18:2 linoleic EFA. Digestive interference may occur if sugar in fruit and sweet vegetables, or greasy foods are consumed at the same time.
7) Refined carbohydrate - sugar and refined grains, added fats and oils, too much fruit, and most commercial breads having added sweeteners, fats, and oils may increase systemic oxidative stress - prodiabetic and atherogenic.
Further discussion shows N-6 and N-3 in proper quantity and proportion can be obtained from whole foods without added oils, vitamin C optimal at 200 mg/day, 1000 iu vitamin D may be desirable for many people, protein requirements to maximize GSH synthesis and reduce inflammation 30% higher than RDA/DRI recommendations, and fish intake having benefits - protein, B-12, iron absorption enhancement, support of skeletal muscle carnitine capacity - and hazards - mercury and other contaminants - especially in fatty fish.

Outline

I. Good Nutrition

II. Digestive Performance

III. Composition

a. General

b. Proatherogenic Factors

c. N-6 and N-3

d. Vitamin C

e. Protein

f. Vitamin D

IV. Other Considerations

a. Flavanoids

b. Nebulizers

c. Hair Analysis

I. Good Nutrition

Whole foods - preferred source of antioxidants - with hundreds of phytonutrients (Frankenfeld 2008, Malik 2007, Rousseaux 2004, Slavin 2003, Prior 2003, Drewnowski 2000, Byers 1995, Ornish 1998, Pritikin 1985)

weight bearing exercise (Booth 2004, Feskanich 2002, Holick 2000, Vico 2000)

and plenty of water - are beneficial - though do not correct MCS.

Major points:

1) 2 lbs nutritious vegetables for C, B2, Folate, A, E, K, Calcium, Potassium, and N-3 18:3 alpha linolenic essential fatty acid (EFA).
2) Marginal vegetables such as beans and tubers may present excessive viscous fiber including pectin - having a flattening effect on the small intestinal villi. Medium chain sugars may increase flatulence and glycoalkaloids in potatoes cause body odor.
3) 3-7 oz meat/fish/poultry provides protein, B-12, iron absorption enhancement, and supports skeletal muscle carnitine transport capacity. Pork and poultry are low in B-12.
4) Whole wheat has high fiber and digestion resistant starch (RS) - too much bulk if consumed to meet all calorie needs. About 1% of the population may be wheat intolerant expressed as celiac disease.
5) Oats have a high proportion of rapidly fermenting viscous fiber - insufficient bulk and fermentation to the distal portion of the large intestine.
6) Brown rice has optimal fiber - nutrients include magnesium, phosphorous, iron, zinc, selenium, B-1, niacin, B-6, pantothenic acid, and N-6 18:2 linoleic EFA. Digestive interference may occur if sugar in fruit and sweet vegetables, or greasy foods are consumed at the same time.
7) Refined carbohydrate - sugar and refined grains, added fats and oils, too much fruit, and most commercial breads having added sweeteners, fats, and oils may increase systemic oxidative stress - prodiabetic and atherogenic.

II. Digestive Performance

Celiac disease - intolerance of wheat, barley, and rye - occurs in about 1% of the population (McGough 2005).

Whole wheat as principle calorie source results in too much fiber and digestion resistant starch (RS) reaching the large intestine.

A high proportion of plant foods predominating in rapidly 90-100% fermenting, viscous soluble fiber such as pectin - relative to those of hydrating, slowly 30-80% fermented cellulose or hemicellulose - may result in small intestinal villous broadening, reduced number of villi, and loss of absorptive surface, suboptimal colonic (large intestinal) fermentation, digestive discomfort, and irregularity (Priebe 2010, Cummings 1987, Paulini I. 1987, Tasman-Jones 1986, 1978, Owen 1977, Chako 1969, Cook 1969).

Studying small intestinal biopsies of South India adults, Baker 1963 found villi were no longer finger-like as present in human fetuses - but instead leaf-like with changes maximal at the duodenum and upper jejunum and contrasting with Western man where similar distortions in villus structure had only been associated with pathological states.

Cook 1969, in biopsy of African jejunal mucosa found villus structure both leaf shaped with normal d-Xylose absorption (grade 2) and leaf shaped coalescing to form short ridges with abnormal d-Xylose absorption (grade 3).

Owen 1977 compared biopsies of San Francisco vegetarians with those on American mixed diets and reported vegetarians showed fusion of the tips, branching, and broadening - but not shortening of the villi - with more plasma cells in the lamina propria and lymphocytes in the villus epithelium compared to the mixed diet group.

Tasman-Jones 1978 confirmed villus alteration in rats and implicated pectin as a likely culprit - number of villi in the jejunal and ilead small intestine:

fiber free 1769 and 3174

fiber free + cellulose 1789 and 3467

fiber free + pectin 1548 and 2802

Despite other unhealthful aspects, the finger-like villi of the newborn remain so in adults consuming traditional Western diets which do not emphasize unrefined plant foods (Owen 1977, Baker 1963).

Africans whose diets predominate in plant foods and vegetarians studied in San Francisco have a broadening of the villus structure with a reduced number of villi (Owen 1977, Cook 1969) thought to be caused by viscous fiber - especially pectin (Tasman-Jones 1986, 1978, Baker 1963).

It appears that hemicellulose of brown rice and cellulose found in both rice and vegetables do not cause broadened villi - which is a loss of absorptive surface (Tasman-Jones 1986,1978).

Pectin has been associated with cell swelling, loss of microvilli, and hemorrhage on the surface of the jejunum. In addition, 7 subjects fed a diet with 20 grams of apple pectin for 4 weeks not only has delayed gastric emptying during that period but also were found to take twice as long to empty the stomach of a pectin free meal following a 16 hour overnight fast (Schwartz 1982).

Fruit, oats, barley, and legumes contribute to a large amount of pectin - and tubers such as carrots, turnips, and potatoes are also suspect. Other vegetables such as cauliflower and brussels sprouts are noted to bring about undesirable digestive symptoms - though perhaps at least partly due to fructose content.These foods also lack the nutrient density of green vegetables.

The viscous fibers in legumes, barley, and oats have been portrayed as the good guys in glycemic index (Jakobsen 2010, , Liu 2000) - but they may be involved with villus structure alteration and causing undesirable digestive symptoms and interference. This area of concern seems to have received little attention - adverse effects due to indiscriminant consumption of fruit, vegetables and grains.

Clearance of a full stomach takes 4 hours by small increments of chyme, 1-5 ml twice per minute - released to the small intestine. 90 minutes later - remaining fiber, RS, and undigested sugars enter the large intestine in a fluid. Optimal substrate provides nourishment and hydration nearly to elimination 36-45 hours later (Olson 1995, Groff 1990).

Large particles of highly fibrous vegetable matter require 100 minute contractions during interdigestive periods to break down and clear the stomach.

Oats predominate in viscous fiber - not supporting optimal fermentation to the distal portion of the large intestine.

Difficulty with beans may be due to viscous fiber and medium chain sugars raffinose and stacchyose.

Tomatoes and orange juice may cause cramping and dropout possibly due to citric acid.

There may be factors concerning oxalic acid - including type of fermentation substrate - not accounted for in studies measuring calcium absorption from vegetables using white bread as accompanying test meal (CVMP 2003, Chen 2002, Holmes 2000, Justice 1985).

Consumed as only vegetable the day before - cabbage may cause mild - and leaf lettuce more severe cramping during strenuous exercise.

Mustard greens may be toxic due to high levels of sinigrin (Drewnowski 2000).

Spinach may be antinutritional due to oxalic acid and polyphenol content (Heaney 1988, Gillooly 1983).

Glycoalkaloids in potatoes may cause body odor (Friedman 2003).

III. Composition

a. General

Online: USDA NUTRIENT DATABASE FOR STANDARD REFERENCE.

Principle to rice are: magnesium, phosphorous, iron, zinc, selenium, B1, niacin, B6, pantothenic acid, and N-6 18:2 linoleic essential fatty acid (EFA).

Vegetables are important for obtaining C, B2, folate, A, E, K, calcium, sodium, potassium, and N-3 18:3 linolenic EFA.

Tomatoes, green peppers, lettuce, cucumbers, celery, and string beans are among those low in many nutrients.

Fruit also lacks nutrients and may present excess fructose.

b. Proatherogenic Factors

Multiple units of glucose make up the starch of rice - metabolized with insulin release and a temporary rise in blood glucose and triglycerides. On contrast, fructose - recognized by its sweetness - does not involve insulin release or blood glucose rise - but triglycerides go up and remain high - increasing heart disease risk - especially in men (Chong 2007, Bantle 2000). Hepatic fructose metabolism results in partitioning of fatty acids towards esterification and impaired triglycerol clearance (Chong 2007).

Glucose as a simple sugar and fructose - or in combination as sucrose - such as in sweetened beverages and fruit juice - and even at low to moderate consumption - is shown to impair glucose and lipid metabolism, increase inflammation - and fructose intake is an independent predictor of a proatherogenic increase of smaller LDL particles (Aeberli 2011, 2007).

The action of excessive dietary fructose on bacterial flora (10% of US calories and often exceeding 20% among America's youth) - in the Western dietary context - and even if not in a weight gain situation - may result in:

lower scores on tight junction protein measures - impacts on intestinal wall integrity - alteration or bloom of bacteria - increased microbrial translocation (MT) from the gastrointestinal tract and endotoxemia - higher plasma endotoxin concentrations (inflammatory cell wall components of gram negative bacteria), soluble CD-14 LPS (lipopolysaccharide endotoxin) receptors, and LPS binding protein-1 (LBP-1),

large elevations in c-reactive protein and liver enzymes - alanine transferase, alkaline phosphatase, and y-glutamyl transpeptidase - LPS overwhelming local and innate immune mechanisms reaching kupffer (liver macrophages) and non immune liver cells producing periportal inflammatory infiltrates - liver damage -

which if accompanied by extra calories leads to Hepatic Steatosis (HS) - today's epidemic of nonalcoholic fatty liver disease (NAFLD) afflicting nearly 1/3 of the US population -

fructose participation in lipogenesis - unlike glucose, not involving insulin - fructose 90% uptake by the liver promoting insulin resistance adversely effecting glucose metabolism disposing to the development of type 2 diabetes and cardiovascular disease (Kavanagh 2013, Hellerstein 2012).

It is widely known that saturated fat, total fat, cholesterol, and refined grains - absent fiber, antioxidants, and other nutrients - are cardiovascular risk factors (Fisher-Wellman 2010, Jakobsen 2010, Siri-Tarino 2010, Delgado-Lista 2008, Klein-Platat 2005, Shi 2005, Andersson 2002, Robertson 2002, Liu 2000, Friedman 1965).

c. N-6 and N-3

N-6 18:2 linoleic and N-3 18:3 linolenic are the dietary essential fatty acids (EFA) - losses noted in MCS patients (Deluca 2010). N-6 can be formed into arachidonic acid. N-3 serves as precursor for synthesis of the Omega 3 fatty acids - eicosapentaenoic (EPA) and docosohexaenoic DHA (DRI 2006).

Because N-6 and N-3 are found in vegetable oils traditionally used in preparation of foods - deficiency is uncommon. However, more often there is either an excess of N-6 enriching lipoproteins and cell membranes creating a pro-oxidant state, or a disproportion beyond the recommended ratio between 5 and 10 to 1 N-6/N-3. Competing for the same desaturase enzymes - too high a ratio may inhibit N-3 synthesis to DHA while too low may limit desaturation of N-6 to arachidonic (DRI 2006).

Adequate N-3 and formation of Omega 3 EPA and DHA is associated with prevention of arrhythmias, reducing atherosclerosis, decrease in platelet aggregation and plasma triacylglycerol concentration, a slight increase in HDL, modulation of endothelial function, and decreasing inflammatory eicosanoids (DRI 2006).
Excessive intake of Omega 3 EPA and DHA - such as supplements - may result in prolonged bleeding time (DRI 2006).

Among added oils - flaxseed is approx 14&50, canola 30&10, and soybean 34&5% of the total composition N-6 and N-3 respectively. Safflower, corn, peanut, and olive oil - while containing 75, 57, 31, and 8% N-6, have little N-3 (USDA 2014, DRI 2006).

Dietary emphasis on whole grain such as brown rice provides a safe level of N-6 and some N-3, cruciferous vegetables bring more N-3 to the right ratio. Most other vegetables - except dried beans and spinach - contain little N-3. The inclusion of fish adds preformed Omega 3 (USDA 2014, DRI 2006).
Adequate intake is estimated 8-16 grams N-6 and 1-1.6 grams N-3, less than 1/2 ounce and a few drops - within the ratio of 5 and 10 to 1 N-6/N-3 - quantity and proportion contained in the whole foods mentioned above.

d. Vitamin C

Known for role as antioxidant - including scavenging reactive oxidants in respiratory mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion (DRI 2006) - most vitamin C is in cells - with a lesser plasma concentration (Padayatty 2003, RDA 1989, Garry 1987, Moser 1987, Kallner 1979). Cells saturate before plasma at intakes between 100 and 200 mg daily with nearly the maximum 2000-3000 mg body store achieved at approx 200 mg/day - though plasma concentrations rise slightly as intakes increase to over 1000 mg/day.

Intakes of 60-100 mg/day result in nearly one half the body store (1500 mg) which at full deprivation may fall into the scorbutic range in 30 days - overt symptoms of scurvy occurring at under 10 mg/day with stores below 300 mg. Low but non-scorbutic plasma vitamin C concentrations may produce fatigue.

90% of 30 mg and less than half a 1250 mg dose is absorbed. At daily intakes of less than 100 mg metabolic byproducts - principally oxalate - are excreted. At intakes over 200 mg much vitamin C spills into the urine as the originally composed ascorbic acid.

Observing the minimal rise in plasma concentration at intakes over 200 mg/day and no change in the marker of oxidative stress (plasma T bars - thio barbituric acid - reactive substances) - Rousseau 2004 concluded the optimal bioavailability of vitamin C seems to be reached at 200 mg/day - higher amounts apparently conferring no additional value with increased energy expenditure.

The DRI has been set at 60-90 mg/day which not reaching maximum saturation - may seem low. 200 mg may be best - fully saturating the cells which comprise most of the store while not resulting in large amounts of ascorbic acid or its metabolites in the urine and feces - reducing risk of undesirable side effects that may occur at higher intakes (Rautiainen 2010, Gomez-Cabrera 2008, DRI 2006).

There is evidence that those with more oxidative stress require higher vitamin C - such as smokers calculated to need an additional 35mg (DRI 2006) and vitamin C losses occur in the storage and preparation of food (USDA 2014). Daily 200mg supplementation of approx 1/16 teaspoon of sodium ascorbate powder or 1/20 teaspoon ascorbic acid powder (synonym:crystals) avoids potential digestive upset by flow agents contained in tablets.

e. Protein

Not including the meat/fish group may result in health problems (Hurrell 2010, Vakur Bor 2010, Navas-Carraterro 2008, Herrmann 2008, Hallberg 1978, USDA #22, #15)

A reduced antioxidant capacity and increased susceptibility to oxidative stress may occur if protein intake is low (Humayan 2007, Jackson 2004) - though increasing protein will not cure MCS.

Glutathione (y-glutamyl-cysteinyl-glycine; GSH) is synthesized from amino acids glutamate, cysteine, and glycine by the sequential action of y-glutamylcysteine synthetase (y-GCS) and GSH synthetase ( Wu 2004, Griffith 1999).

GSTM1 and GSTT1 - objects of the Deluca and Schnakenberg studies - concern the activation of Phase II enzymes known as GSH-S-transferases (GST) which catalyze the reaction of Glutathione (GSH) with electrophiles - a broad class of xenobiotic and endogenous compounds - including environmental toxins and reactive oxygen species (Block 2011, Manfredi 2009, Hayes 2005, Wu 2004, Griffith 1999).

In a condition such as MCS GSH depletion may be inevitable (Deluca 2010) either by excess utilization in spontaneous or GST catalyzed reactions or by suppression of synthesis such as with high levels of NO production (Lu 2009, Oslund 2008, Darmaun 2005, Wu 2004, Canals 2003, Griffith 1999, Sterner-Kock 1999, Tanabe 1996).

Adequate dietary protein - including provision of the precurser amino acids glutamate, glycine, and especially the sulfur containing amino acids cysteine and methionine - is critical for the maximization of GSH synthesis (Sekhar 2011, Lu 2009, Jackson 2004, Lyons 2000, Bella 1999, Jahoor 1995, Grimble 1992). Cysteine is considered a semi-essential amino acid because it can also be derived from methionine - an essential amino acid (Griffith 1999a).

Sekhar 2011 reported that by supplementing elderly volunteers with glycine and approx 1000 mg cysteine in the form of n-acetylcysteine per 150 lb body weight (.81 mmol kg-1 d-1) - GSH levels improved and oxidant concentrations decreased -

GSH: 39 yr old controls 2.08 mmol/L RBC, elderly before supplement 1.12 after 2.18 mmol/L RBC.

Oxidant Concentrations: isoprostanes controls 97.2, elderly before 136.3 after 84.8, lipid peroxides controls 1.86, elderly before 6.03 after 3.00.

These oxidant concentrations are expected elevated in MCS (MCS acc, Deluca 2010, Terlecky 2006, Kennedy 2005).

The 1000 mg / 150 lb body weight n-acetylcysteine supplementation of Sekhar 2011 is nearly the combined total of cysteine (273mg) and methionine (755mg) in 3 1/2 oz 100% light tuna in water (no added soy). The elderly often consume less protein than those younger and recent research using the indicator amino acid method holds that the RDA/DRI for protein has been 30% underestimated (Elango 2011, (Humayan 2007, Jackson 2004).

Earlier estimates of adult protein requirement at 55 grams/day include 2000-3000 mg cysteine and methionine. An improved intake of 80-100 provide 3200-4200 - similar to the 1000mg supplement difference in the Sekhar study.

3 1/2 oz tuna rather than a supplement increases total protein (25 grams), adds 3 mcg B-12 (Hermann 2008) which exceeds the RDA and approaches the optimal 4-7 mcg suggested by Vakur Bor 2010, provides non heme iron absorption enhancement (Hurrell 2010, Navas Carraterro 2008), may prevent loss of skeletal muscle carnitine transport capacity as may occur in vegetarians (Stephens 2011), and contains 300mg of preformed EPA and DHA omega-3 fatty acids.

Ramon 2009 indicated that much toxicity of fish may have to do with ocean contaminants - other than mercury - found in fatty fish - with lean fish producing better birth outcomes than diets not containing fish - even though blood cord levels of mercury were higher among all those consuming fish.

Lowest tuna mercury levels are of canned light from the Indian and Pacific Oceans (Sunderland 2007) such as Natural Sea, Natural Value , and Ocean Naturals (Thailand). Canned white (albacore) has nearly 3 fold the mercury of light (skipjack and yellowfin - with skipjack the least) and fresh tuna from the Atlantic have 2-5 times higher levels depending on the variety. Cod and haddock are lean with mercury levels close to light tuna (FDA 2010).

Beef, pork, and poultry have cysteine and methionine amounts similar to that of fish - though contain higher saturated fat and cholesterol. Pork and poultry are low in B-12 (USDA).

Per three and a half ounces:

light tuna canned/water B-12 (mcg) 2.9 Chol (mg) 40

beef round separable lean 1.5 77

pork all .7 84

turkey breast .39 83

chicken " .34 85

Brown rice has nearly as much methionine - but is lower in cysteine - compared to wheat - but the greater fiber and digestion resistant starch of whole wheat limits its consumption due to excess bulk - so that prepared breads typically consumed - not 100% whole wheat - have little more cysteine per calorie than rice.

Mercury amalgam has a strong association with exascerbation of MCS (Pigatto 2013). However, it is not clear whether exposure from fish containing relatively low amounts of mercury has a net adverse effect on MCS - especially considering nutritional disadvantages of not including fish. Mercury is considered the most toxic nonradioactive element - partly because it bonds irreversibly with cysteine thiol groups (Mutter 2007) - suggesting mercury is a powerful TRPA1 agonist - reversibility of bonds formed considered a major determinant of TRPA1 agonist potency (Bessac 2008).

f. Vitamin D

Caucasian skin may have evolved with the northern movement of humans over thousands of years. The light color - minimum melanin - allows picking up maximum UV rays for vitamin D synthesis - and storage life in tissue and plasma allows for 100 days of weaker winter sunshine which will not generate vitamin D. However, it seems that with a longer lifespan the lighter skin is often not durable enough to take sun exposure necessary to maintain optimal vitamin D without skin damage or cancer. It may be possible to obtain vitamin D exclusively from the sun safely - but for many individuals and circumstances a supplement may be needed.

Generally, supplements may not be a good idea because they present a concentration out of natural matrix that may interfere with metabolism of other nutrients - or present a toxic effect.

Antioxidant vitamin supplementation has been reported lacking efficacy (Czernichow 2009, Meydani 2009, Song 2009, McCormick 2006, Bleys 2006, Byers 1995).

Vitamin D may be an exception because of the peculiar dilemma posed in obtaining the vitamin.

With minimum sun exposure - a starting point of plasma 25OH-D at approx. 20 nmol/L, 1000 iu daily supplement vitamin D3 in liquid softgels may be appropriate. The tablet form contains processing ingredients such as magnesium stearate and silica that may cause intestinal upset.

With some sun exposure (low average) take less - such as approx 800 iu.

If lots of time in the sun - supplemental vitamin D may not be necessary.

The sun will not promote vitamin D synthesis 20 days annually for every 70 miles north of 40 degrees latitude at 5000 feet (ex. Denver) or 20 days for every 70 miles north of 35 degrees at sea level. Each 1000 feet of altitude = 70 miles = 1 degree of latitude. For example, 45 degrees north at 5000 feet and 40 degrees north at sea level (ex. Philadelphia) there are approx. 100 days each year with no vitamin D synthesis from the sun (approx. Nov 1 - Feb 10). However, the vitamin is stored in tissue - and plasma 25OH-D gradually decreases.

IV. Other Considerations

a. Flavanoids

Datla 2007 indicates that plant flavonoids vary in effectiveness. It might be helpful to know which plant foods are most effective (Frankenfeld 2008, Prior 2003).

b) Nebulizers

Nebulizers have been used to cover the nerves - some containing antioxidants and xenobiotic enzymes - or expectorants (guaifenesin) to increase fluid and clearance in the airway - with side effects as may be expected.

Dextromethorphan has been prescribed to block symptoms - but cannot be taken on a regular basis.

c) Hair Analysis

Methods for reducing toxic load usually do not address the cause and effect of MCS - and measurements such as hair analysis can be deceiving:

SIEDEL S. ET AL. ASSESSMENT OF COMMERCIAL LABORATORIES PERFORMING HAIR MINERAL ANALYSIS. JAMA 285;67-72 2001:

This study performed by the California Department of Health included 6 laboratories representing 90% of all analyses.

"...laboratory differences in highest and lowest reported mineral concentrations for the split sample exceeded 10 fold for 12 minerals...hair mineral analysis from these laboratories was unreliable..."

For example, with laboratories labeled A to F:

Mercury A) 0.1 , B) 0.9 , C) 0.32 , D) 0.4 , E) 2.0 , F) 0.1

rated high by lab E and normal by labs A,B,C,D,& F with results varying widely.

Lead A) 0.2 , B) 13 , C) 1.3 , D) 0.3 , E) less than 1 , F) 0.76
in extreme error by lab B, rated high by lab C, and normal by labs A,D,E,& F.

Phosphorus was rated high by lab B and low by lab A.

Molybdenum was rated high by lab D and low by labs A & E...

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