Multiple Chemical Sensitivity: 2021 Consensus Criteria Part IV Baseline: Nutrition and Exercise

[michael edward badolato jr]

Multiple Chemical Sensitivity: 2021 Consensus Criteria 

Baseline, Diagnosis, Patient Rights, Etiology 

Part IV Baseline: Nutrition and Exercise

Expertise from the most Prestigious Academic, Medical, and Government Research Facilities

Outline

I.   Baseline GSAA, ACA, SRPE 1-8

II.  Diagnosis, Patient Rights, Etiology 9-14

III. Baseline: Nutrition and Exercise 15-31

     A. SJF, LE 15-20

     B. Whole Food Nutrition 21-31

IV. Baseline: Nutrition and Exercise 32-38

     C. Suboptimal Actors 32

     D. Maintaining Bone Density 33-37

     E. Preventing Atherosclerosis 38

Outline Expanded IIIA,B, IVC,D,E

III Baseline: Nutrition and Exercise 

     A. SJF, LE 15-20

         15. Impaired Capillary Circulation

         16. Dietary Fat: Cancer 

         17. Cordain 2005

         18. GSAA, ACA, SRPE, SJF, LE

         19. Specified Junk Food (SJF) Defined

         20. Prevention and Reversal

     B. Whole Food Nutrition 21-31

         21. Gram/Calorie Conversion

         22. Fructose Lipogenesis

         23. Hemoglobin: Iron Absorption

         24. Protein: GSH Synthesis

         25. Digestion: Wheat, Rye, Barley

         26. Viscous Fiber: Villus Flattening

         27. Nutrients in Matrix

         28. N-6 and N-3 EFA

         29. Vitamin C: 200-300 mg?

         30. Nutrigram

         31. Vegigram

IV. Baseline: Nutrition and Exercise

     C. Suboptimal Actors 32

     D. Maintaining Bone Density 33-37

         33. Acid Base Balance

         34. Calcium: Adequate Not Excessive

         35. Salt: A Small Amount

         36. Vitamin D: 1000 iu Soft Gel - Safe Upper Limit?

         37. Summary: Bone Health, Postmenopause

     E. Preventing Atherosclerosis 38

Abbreviations

     SJF: Specified Junk Food

     LE: Lack of Weight Bearing (Walk, Run) Exercise

     Kcal: calories

IV. Baseline: Nutrition and Exercise 32-37

     C. Suboptimal Actors 32

     D. Maintaining Bone Density 33-37

     E. Preventing Atherosclerosis - 38

32. Suboptimal Actors

MERCK 1999 pg 275-76: "...No bodily function is more variable and subject to extraneous influences than defecation...increased osmotic load...osmotic diarrhea occurs when unabsorbable, water soluble solutes remain in the  bowel, where they retain water...eating too much of some foods, such as certain fruits can produce osmotic diarrhea..."

Collard greens and kale most pleasant - broccoli florets, brussels sprouts, cauliflower, third, fourth, fifth, increase osmotic load, nutrients incomplete - not good stand alone consecutive days - broccoli stalks may be harsh or irregular.

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 and osmotic load.

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

Mustard greens may be toxic, including stomach discomfort, due to high levels of sinigrin; data reported by Drewnowski 2000.

Spinach may be adverse: oxalic acid and polyphenol content (Heaney 1988, Gillooly 1983); and promoting a foul stool.

However, there may be factors increasing calcium availability from oxalic acid containing vegetables - including a more optimal 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).

Potatoes are weak nutritionally except for potassium; glycoalkaloids chaconine and solanine may be source of potato body odor (though not confirmed) and result in formation and rising plasma levels of solanidine, a steroidal aglycone, of concern because affects hormones: breast cancer risk and liver weight increase. Safe level is proposed not to exceed approx 1 mg per 2 pound body weight: 70 mg per 140 pound adult. At 14 mg per 5 ounce potato the average daily potato intake limit would be 25 ounces (Friedman 2003). Tomatidine, the milder aglycone of tomatoes, may also produce body odor (unconfirmed).

IVD. Maintaining Bone Density 33-37

        33. Acid Base Balance

        34. Calcium: Adequate Not Excessive

        35. Salt: A Small Amount

        36. Vitamin D: 1000 iu Soft Gel - Safe Upper Limit?

        37. Summary: Bone Health, Postmenopause

33. Acid Base Balance

Electrolyte: affecting nerve transmission, muscle contraction, and vascular tone; supporting activity level and lean muscle mass; potassium is also important with conjugate anion such as citrate: these intestinally absorbed potassium salts of organic acids are converted to bicarbonate, found mostly in vegetables and fruit, buffer sulfuric acid production from protein metabolism (DRI 2006, Frasseto 1991); potassium chloride of processed foods does not act as a buffer (DRI 2006).

The function of the kidney is to conserve filtered bicarbonate and excrete acid. Low dietary potassium indicates greater renal net acid excretion (RNAE); high sodium intake (salt): both increase calcium loss (DRI 2006).

In the potential renal acid load formula (PRAL) acid contributors are sum of:

    .49 x protein gram/day and .37 x phosphorous mg/d;

for base (alkaline):

    .021 x potassium mg/d, .026 x magnesium mg/d, and .013 x calcium mg/d (Remer 2003).

The PRAL formula approximates RNAE in mEQ/d: a net acid excretion of less than 50 mEQ/d considered acceptable and above 120 mEQ increases calcium loss.

RNAE can be estimated quickly using data predetermined by the PRAL formula in mEQ per 100 kcal (calories) with minus sign (-) indicating base (alkaline) as follows.

     acid: fish 14.6, meat 12.4, poultry 7.8, egg 7.3, shellfish 7.3, cheese 3.3, milk 1.3, grain 1.1

     base: legumes -0.4, nuts -1.1, fruit -5.2, tubers -5.4, root -17.1, veg fruit -17.5, leafy greens -23.4, plant stalk -24.9

     acid: an additional 32.9 mEQ metabolic acid production independent of diet

The data show stalks and leaves of green vegetables are excellent for acid base balance.

mEQ per 100 kcal: 2500 kcal brown rice at 1.1 acidic = 27.5 mEQ acidic; 5 ounces fish 150 kcal = 1.5 x 14.6 = 21 mEQ acidic; independent acid load = 32.9 acidic; adding the three 27.5 + 21 + 32.9 = 81.4 acidic

     24 ounces green veg 200 kcal = 2 x -24 = -48 base

     total acid 81.4 - 48 base = 33 RNAE

     36 ounces green veg 300 kcal = 3 x -24 = -72 base

     total acid 81.4 - 72 base = 9.4 RNAE

Both 33 and 9.4 RNAE are in acid base balance below 50mEQ/d.

American diets acidogenic, 75-100 mEQ/d RNAE; the more alkalinity may be better (Dawson-Hughes 2008), however, as noted in Pt 26, excessive rapidly fermenting viscous soluble fiber of vegetables and fruit - in proportion to the slowly fermenting spongy hemicellulose and lignins of whole grain rice may present increased large intestine osmotic load and small intestinal villus flattening.

34. Calcium: Adequate Not Excessive

Calcium found in extracellular fluids, intracellular structures, and cell membranes; plays an essential role in such vital functions as nerve conduction, muscle contraction, blood clotting, and membrane permeability (RDA 1989).

Many factors influence calcium balance and bone loss: phosphorous, copper, zinc, magnesium, flouron, silicon, boron, potassium, sodium, protein, genetics, sex hormones, weight bearing activity level, and vitamin D (RDA 1989). If entirely covering up from the sun take 1000 iu average daily in soft gels to avoid digestive upset from flow agents in tablets (not certain safety of 1100-1400 or adequacy at 800). If getting some sun - maybe 600 iu or less; lots of sun - don't take supplemental D3. 

Weight bearing activity has a large influence on calcium balance and bone density (Booth 2004, Vico 2003, Welton 1994, RDA 1989). Running produces greater bone density than walking, though both are good for bone health. Post menopausal women walking at least 4 hours per week had 41%, 8 hours or more 55% lower risk of hip fracture than those walking less than 1 hour per week (Feskanich 2002).

Sedentary behavior guarantees negative calcium balance and bone loss regardless of nutrient intake.

MERCK 1999 pg 470-471: "...Increasing physical activity may increase bone mineral density and lead to increased stability and muscle strength...Physical stress tends to increase bone mass, whereas immobilization furthers bone loss...The risk of fractures is reduced by non pharmaceutical measures...increased walking and other weight bearing exercises..."

Calcium absorption varies: age and physiological demand - at higher intakes a lower percentage is absorbed. During childhood bone accretion, absorption may reach 75% (RDA 1989). Adults absorb less than 15% of dietary calcium over 800 mg/day, 20-40% overall. Urinary 100-250, fecal 100-150 not including unabsorbed dietary calcium, and sweat 15-20; loss totals 215-420 mg/day - wide variation (RDA 1989). It appears often not lack of intake - instead what increases calcium loss or misutilization.

Increasing vegetables and fruit from 12 oz to 34 oz/d - contributing bicarbonate precursors to the acid base economy - principally potassium with its anions, along with nutrients including calcium and magnesium - reduced urinary calcium loss from 157 to 110 mg/d (New 2002, Appel 1997).

1000 mg/d compared to 500 during child and teen bone accretion correlate with greater bone mass during adulthood and less risk of fractures (Kalkworf 2003, Matkovik 1995, RDA 1989, Arnaud 1988, Heaney 1986). Studies comparing intake during adulthood show relatively little effect on bone status - although a small but consistent positive correlation may exist especially when baseline calcium was low (Bolland 2015, Cumming 1990, RDA 1989, Freudenheim 1986, Garn 1970, 1969). Calcium balance is resistant to calcium intake changes in the range of 415-1740 mg/d (Hunt 2007). Calcium intake was not associated with hip fracture risk in men and women.

Including 1 lb/d greens (kale or collards) 400-500 mg calcium, 200 in other vegetables (brussels sprouts, cauliflower), and 200-300 mg from 2000-3000 kcal brown rice abundant source of phosphorous, copper, zinc, and, magnesium (USDA) - bring the total calcium to 800-1000 mg/d.

Calcium absorption % of total calcium: spinach 5% (Heaney 1988), milk 27-46% (Heaney 1993, 1990, 1988), kale 40-52% (Heaney 1993, 1990), broccoli and bok choy 47-52% (Heaney 1993), sweet potatoes 42%, chinese spinach and rhubarb 23-25% (Weaver 1997) - however, there may be factors increasing calcium availability from oxalic acid containing vegetables - including a more optimal 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).

Calcium supplementation - not recommended - may inhibit absorption of iron, zinc, and other essential nutrients; increase hip fracture risk by causing phosphate deficiency (Bischoff-Ferrari 2007); contribute to urinary stone formation; add 13-23% to cardiovascular disease risk (Bolland 2011); and very large amounts - hypercalciuria, hypercalcemia, and deterioration in renal function (DRI 2006, RDA 1989).

35. Salt: A Small Amount

Excessive sodium - requirement less than 1000 mg/day - average American consumption is over 3200, readily obtained from salt (sodium chloride): thirst, water retention in extracellular space, hypertension (high blood pressure), arterial stiffness, heart left ventricular hypertrophy, reduced renal function (Farquhar 2015, RDA 1989); and together with concentrated calories: sugar, refined grains, fats, oils - a growth promoter, and calcium loss is increased: for every gram excess sodium the kidney must excrete, 26 mg calcium is lost (Itoh 1996, Devine 1995, Matkovic 1995, Palmieri 1995, Zarkadas 1989, Shortt 1988, Castenmiller 1985, Nordin 1993) - although perhaps not large cause of bone resorption, reduced bone mass, or osteoporosis unless sodium intake is very high (Lin 2003, New 2002). 

Higher stomach cancer rates of the past may have been due to greater consumption of salt preserved foods.

Obligatory dermal, urinary, and fecal sodium losses are minimal: approx 115 mg/d  (DRI 2006, RDA 1989), the body is stingy - high losses in sweat are more likely to reflect excessive intake rather than critical loss - there is little or no evidence of deficiency at low intakes (DRI 2006).

Sodium and chloride wide distribution in vegetables, grain, and fish (DRI 2006) is close to meeting requirement without adding salt. However, it may be a good idea to include a small amount - about as in salted canned tuna in water. If adding salt, only quarter teaspoon (1-2 grams): well dissolved, diluted, mixed.

The total sodium requirement and preferred intake is less than 1000 mg, perhaps closer to 500; DRI set at 1500 mg which may be excessive: rationale that with predominance of salted food products, setting the DRI lower might be impractical. 

36. Vitamin D: 1000 iu Soft Gel - Safe Upper Limit?

The sun will not promote vitamin D synthesis 20 days annually for every approx 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 serum and tissue; 25(OH)D and D3 gradually decrease.

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, with subsequent storage in serum and tissue. 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.

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.

There is uncertainty; reading this article carefully may help in making decision. If entirely covering up from the sun take 1000 iu average daily (not certain safety of 1100-1400 or adequacy at 800 iu), in soft gels to avoid digestive upset from flow agents in tablets. If getting some sun - maybe 600 iu or less; lots of sun - don't take supplemental D3.

Vitamin D (calciferol) and resulting D metabolites are active via receptors throughout the body (NIH), and essential in proper formation of the skeleton and mineral homeostasis. Roles in cellular metabolism include antiproliferation and prodifferentiation actions (DRI 2006). The biologically active form 1,25(OH)2D and parathyroid hormone (PTH) regulate and maintain intestinal absorption and serum levels of calcium and phosphorous.

D3 (cholecalciferol) is the principle, though relatively inert, initiating form of vitamin D. Ergocalciferol (D2), not so important to this discussion, is from ultraviolet conversion of ergosterol in plants. Both D3 and D2 have been used in fortified foods.

Exposure to short wave ultraviolet B rays (DRI 2006) catalyzes synthesis of vitamin D3 from 7-dehydrocholesterol in the skin. Supplemental (dietary) D3 is carried in chylomicrons, and D3 from the skin in the blood bound to protein and albumin; either way to the liver where D3 is hydroxylated to 25(OH)D (calcidiol) at a limited conversion rate (Heaney 2008). Serum levels of 25(OH)D also known as 25 hydroxyvitamin D, indicator of vitamin D status, 2 units of measure have been used: 1ng/ml equals 2.5 nmol/l. In becoming more biologically active 25(OH)D is hydroxylated to 1,25(OH)2D (calcitriol) in the kidneys, tightly regulated by PTH in response to serum calcium and phosphorous levels; while both 25(OH)D and 1,25(OH)2D levels vary greatly among individuals having similar sun exposure or supplement dosage: 25(OH)D goes up or down in response to dose; whereas 1,25(OH)2D has no seasonal variation (DRI 2006, RDA 1989).

D3 stores persist in fat depot and skin; inactivated metabolites are excreted in the bile and urine. D3 from the sun does not reach toxic levels: a limited amount is formed, beyond which previtamin and vitamin D3 remaining in the skin are destroyed with continued sun exposure.

With D3 supplements: no limit of potential toxicity, only caution in determining appropriate dosage, which has involved much consideration.

The NIH Fact Sheet has reported 75-120 nmol/l serum 25(OH)D associated with increased all cause mortality, more falls and fractures among the elderly, cardiovascular events, and greater risk of some cancers - especially pancreatic.

On contrast, improved bone mineral density (BMD), fewer fractures and falls (Bischoff-Ferrari 2009, 2007, 2004a, Cashman 2008a, Viljakainen 2006a, Lehtonin-Veromaa 2002); better physical performance and low extremity function (Wicherts 2007, Bischoff-Ferrari 2004b); reduced type 2 diabetes, influenza susceptibility, and cancer risk (Liu 2010, Urashima 2010, Lappe 2007) - improvements found to occur as serum 25(OH)D rises above 50 nmol/l, continuing up into the 60's, and possibly to 72 nmol/l: supported by average daily dose 600-1400 iu.

Because of decreasing dose response at higher intakes, it requires nearly doubling from 1400 to 3000 iu in going 72 to 80 nmol/l serum 25(OH)D. PTH (parathyroid hormone) elevation is thought in response to low calcium intake or low vitamin D stores, and PTH has been found to not level off until 25(OH)D reaches 80 nmol/l (Cashman 2009, 2008b, Lappe 2006, Bischoff-Ferrari 2004a, 2004b) - therefore some believe 80 nmol/l may be optimal. That may feel good summer day in the sun, but maintained by a large increase in supplemental dose year-round: not so sure.

On the side of caution, and no clear evidence of great advantage to being at 80 nmol/l compared to 72, other than PTH leveling: it may be better to keep D3 intake at 1000 iu if entirely covering up from the sun. 

Caucasians had approx 92 nmol/l serum 25(OH)D compared to Asians approx 62 nmol/l in the same abundant year round Honolulu sun exposure (Binkley 2007). At far enough north or south latitude, caucasian 92 nmol/l 25(OH)D supported by seasonal summer sun may drop to 42 nmol/l in winter. Asian year round hawaiian sun, approx 62 nmol/l: does this suggest supplementation appropriate group average would be closer to the Asian value 62 nmol/l, so that 60-72 makes more sense than 75 and above?

Reluctant to go higher out of safety concerns: the RDA 1989 was set 200-400 iu, DRI 2006 at 400, DRI 2010 to 600; 800 iu for age 71 and above; however, there has been calling for a somewhat higher recommendation: 600 iu may barely reach 60 nmol/l 25(OH)D.

DRI 2010 Figure 5.4, Aloia 2008, Heaney 2008, Viljakainen 2006b - point to a nearly biphasic dose response of skin produced or supplemental D3 liver hydroxylation to serum 25(OH)D: first order is nearly complete conversion of D3 to 25(OH)D up to D3 saturation limit of liver hydroxylation enzymes, beyond which, called zero order, Heaney 2008 estimated conversion rate 43% of D3 hydroxylated to serum 25(OH)D, the remaining 57% to accumulate in serum and body fat. Inconsistent lab measurement methodology has made estimating first order saturation limit difficult: Heaney 2008 suggested 2000 iu D3 supporting 88 nmol/l 25(OH)D saturation limit, which seems high compared to DRI 2010 Figure 5.4 and Viljakainen 2006a: approx 800-1400 iu at 65-72 nmol/l.

In context of D3 supplementation, at physiologic intakes up to near complete conversion to 25(OH)D saturation limit, the principal storage form of vitamin D is serum 25(OH)D, levels increasing with dose, outpacing kidney hydroxylation of 25(OH)D to the more biologically active 1,25(OH)2D mentioned earlier. The supplemental dose becomes supraphysiologic when it goes beyond the first order saturation limit, resulting in accumulated stores of serum D3 in serum and body fat. Therefore cautious, maybe the supplemental dose should be slightly below, or not far beyond, the first order saturation limit estimated to be 800-1400 iu at 65-72 nmol/l; the dose lower if receiving sun exposure.

With UVB cutaneous (skin) synthesis of D3, it is natural to increase both 25(OH)D and D3 stores - it is physiologic in that accumulated D3 is drawn down from serum and body fat during the weak winter sun season at latitudes far enough north or south of the equator.

Approximation of dose response, adapted from DRI 2010 Figure 5.4 (and similar conclusions Aloia 2008, Viljakainen 2006b) has a large confidence interval (Ci) of uncertainty. It seems relatively sure the goal is supplemental D3 as required to achieve serum 25(OH)D somewhere, not certain precisely, between 60 and 72 nmol/l average for group; and taking into account large dose response Ci, not sure the precise amount to take.

Starting point minimum sun exposure: daily supplemental dose 0 iu = 20 nmol/l serum 25(OH)D.

600 iu average daily dose 0 iu = 20 nmol/l (starting point) rises to 60 nmol/l (Ci 52-68)

    add 200 (total 800 iu) = 65 nmol/l (Ci 57-73)

800 iu may be a little low?

    add 200 (1000 iu) = 68 (60-76)

if entirely covering from the sun, 1000 iu may be an appropriate dose, or

a shade high at Ci 76

    add 200 (1200 iu) = 70 nmol/l (62-78)

    add 200 (1400) = 72 (64-80)

not sure 1200 and 1400 are safe

at this point the dose response has decreased to a slow 2 nmol/l per 400 iu

    add 400 (1800 iu) = 74 (66-82)

    add 400 (2200) = 76 (68-84)

    add 400 (2600) = 78 (70-86)

    add 400 (3000) = 80 (72-88)

It takes 1600 iu to go from 72 to 80 nmol/l serum 25(OH)D: 1400 iu increased to 3000.

A maintained increase in dosage causes 25(OH)D to rise steeply the first 4 weeks - then less so - before 25(OH)D plateaus at 6 weeks (Harris 2002).

With plenty of sun exposure there are individuals having what are considered deficient serum 25(OH)D levels. Cause of the well established large variability in dose response is not fully understood. Duncan 2012 reported if the systemic inflammatory response is elevated - reflected by plasma C reactive protein greater than 10 mg/l - then potential for decrease in 25(OH)D makes vitamin D status based on plasma measurements not reliable. Keeping in mind 25(OH)D is only an indicator - 1,25(OH)2D is considered the more biologically active form - it may not be a good idea to adjust D3 supplemental dose to obtain a serum 25(OH)D level, at least not too much, instead better to go on the research determined optimal average for the group - thought to be appropriate and safe.

Repeating earlier Vitamin D3 supplement in soft gels recommendation:

There is uncertainty - reading this article carefully may help in making decision. If entirely covering up from the sun take 1000 iu average daily (not certain safety of 1100-1400 or adequacy at 800 iu), in soft gels to avoid digestive upset from flow agents in tablets. If getting some sun - maybe 600 iu or less; lots of sun - don't take supplemental D3.

37a-i. Summary: Bone Health, Postmenopause

a. It likely takes a perfect score of nutrition and exercise factors to maintain bone and joint health.

b.The difference between 34 oz vegetables per day and 12 oz includes nutrient deficiencies and approx 45 mg/d increased urinary calcium loss. Vegetables provide necessary alkalinity so that renal net acid excretion (RNAE) is not excessive. (33,34)

c. Each gram of excess sodium excreted (usually from too much salt) pulls out 26 mg of calcium. (35)

d. There is uncertainty; reading (36) Vitamin D 1000 iu Soft Gel - Safe Upper Limit? may help in making decision. If entirely covering up from the sun take 1000 iu average daily (not certain safety of 1100-1400 or adequacy at 800 iu), in soft gels to avoid digestive upset from flow agents in tablets. If getting some sun - maybe 600 iu or less; lots of sun - don't take supplemental D3.

e. Adults absorb less than 15% of dietary calcium over 800 mg/day, 20-40% overall. Urinary 100-250 mg, fecal 100-150 not including unabsorbed dietary calcium, and sweat 15-20; loss totals 215-420 mg/day - wide variation (RDA 1989). It appears often not lack of intake, instead what increases calcium loss or misutilization. Calcium supplementation - not recommended - may inhibit absorption of iron, zinc, and other essential nutrients; increase hip fracture risk by causing phosphate deficiency (Bischoff-Ferrari 2007); contribute to urinary stone formation; add 13-23% to cardiovascular disease risk (Bolland 2011); and very large amounts - hypercalciuria, hypercalcemia, and deterioration in renal function (DRI 2006, RDA 1989). (34)

Micronutrients (vitamins, minerals) are best dispersed in whole food matrix along with many other substances that facilitate or regulate absorption. Nutrigram and vegigram provide data (USDA SR28) in choosing nutritious vegetables. (30,31)

f. Dietary fat over 10% of calories may reduce blood flow through fine capillaries important to bone and joints. (15,20)

g. Regardless of nutrition, weight bearing exercise (walk, run) is necessary to stimulate bone density and circulate joints. (20.34)

h. Premenopausal natural estrogen levels may cover bad habits; postmenopausal may reduce protection.

i. Along with minerals important to bone health (30,31,33,34) - brown rice and brassica vegetables contain phytoestrogens including lignans found to decrease breast cancer risk (Buck 2010); whereas estrogen hormone replacement therapy increases endometrial and breast cancer risk (Merck 1999).

Lignans including matairesinol (MAT), secoisolariciresinol (SECO), and their glycosides - are transformed by large intestinal bacteria to the mammalian lignans: enterolactones and enterodiols (Rodriguez-Garcia 2019, Wang 2002, Tham 1998).

American Cancer Society statement published in World Almanac Book of Facts 2008:

"... Most studies suggest that long term use (5 years or more) of hormone replacement therapy (HRT) after menopause increases the risk of breast cancer, and recent studies suggest that risks from taking HRT exceed benefits..."

MERCK 1999 1943:

"...there is evidence relating estrogen to breast cancer...in women who have a uterus, unopposed estrogen therapy increases the risk of developing endometrial cancer..."   

IVE. Preventing Atherosclerosis 38 

Affecting brain, heart, kidneys, other vital organs, and extremities; atherosclerosis produces most coronary heart disease (CHD) and ischemic stroke - combined number one killer in western countries.

Atherosclerosis increases in postmenopausal women and approaches that in age matched men (Merck 1999).

MERCK 1999 1655-56:

"...The earliest detectable lesion of atherosclerosis is the fatty streak (consisting of lipid-laden foam cells, which are macrophages that have migrated as monocytes from the circulation into the subendothelial layer of the intima), which later evolves into the fibrous plaque (consisting of intimal smooth muscle cells surrounded by connective tissue and intracellular and extracellular lipids)...

...the atherosclerotic plaque may grow slowly and over several decades may produce a severe stenosis or may progress to total artery occlusion. With time the plaque becomes calcified. Some plaques are stable, but others, especially those rich in lipids and inflammatory cells (eg macrophages) and covered by a thin fibrous cap, may undergo spontaneous fissure or rupture, exposing the plaque contents to flowing blood. These plaques are deemed to be unstable or vulnerable and are more closely associated to the onset of an acute ischemic event. The ruptured plaque stimulates thrombosis; the thrombi may embolize, rapidly occlude the lumen to percipitate a heart attack or acute ischemic syndrome (transient ischemic attack [TIA] or ischemic stroke), or gradually become incorporated into the plaque, contributing to the stepwise growth..."

Consistent with Merck 1999; Pritikin 1990 summarized atherosclerosis resulting from SJF: at birth arteries have no plaque, age 10 fatty streaks, 20 fibrous plaque, 30 a complicated lesion, 40 lesion calcified, 50 and beyond narrow arteries, degenerative features, critical stage - possible myocardial infarction (heart attack), stroke, claudication, gangrene , aneurism, senility, and other difficulties.

Cholesterol intake over 100 mg/day, added fats and oils beyond naturally occurring in vegetables, fruit, and grain - except nuts, seeds, olives, avocados, and soybeans are too high in oil - raising the fat calorie percentage above 10% - and with sugar, refined grain, and excessive salt (sodium beyond 1500 mg/day) - comprise specified junk food (SJF) - in agreement with Pritikin 1990, 1979.

Better 80-8-12 carbohydrate, fat, protein % of calories: fine capillary delivery is restored in 72 hours (Swank 1961), arterial plaque is cleared in 1-2 years (Ornish 1998). And work towards a minimum 6 miles a day (2 hours) walking and running - referred to as weight bearing exercises for good health - including strong joints and bones.

Unrefined whole food (Malik 2007, Slavin 2003) less than 10% calories in fat, cholesterol intake under 100 mg/day - supports total blood cholesterol under 160 ng/dl - nearly impossible to develop atherosclerosis (Ornish 1998, Pritikin 1990, 1979).

MERCK 1999 1659-60: "...the average US diet contains 37% of total calories in fat. The American Heart Association recommends the proportion be reduced to 20%, yet a reduction to less than 10% may be needed to have a major effect on CAD risk..."

MCS Consensus Postscript Splash:

    I.   Ambient Combustion Aerosol (ACA) Composition

    II.  MCS, ME/CFS - Inflammatory Response to Air Pollution

    III. Macronutrients - Starch Preferred Energy

    III. Micronutrients - Vegetables Essential

IV. ACA PM Gastro-Inflammation, Vagal Circuitry

MERCK 1999:
"...Crohn's disease and ulcerative colitis are characterized by chronic inflammation of various sites in the GI tract. Both cause diarrhea which may be profuse and bloody...evidence suggests that a genetic predisposition leads to an unregulated intestinal immune response to an environmental, dietary, or infectious agent..."

ANANTHAKRISHNAN 2011:
"... Inflammatory bowel diseases (IBDs) refer to two chronic intestinal inflammatory disorders, Crohn's disease (CD) and ulcerative colitis (UC), which typically have their onset during young adulthood (Abraham 2009). Together, these affect an estimated 1.4 million people in the United States (Abraham 2009) and account for over $6 billion USD in direct health care costs (Kappelman 2008). This past few decades have seen a striking increase in the incidence of IBD (Loftus 2000, 1998) and the number of IBD-related hospitalizations (Bewtra 2007)...
...Known genetic variations account for less than 25% of IBD risk (Abraham 2009)...
...The incidence of IBD has increased relatively rapidly over the past few decades, which cannot be explained through genetic mechanisms (Lakatos 2009, Koloski 2008, Danese 2004, Loftus 2000, 1998). Moreover, this increase has been particularly striking in several developing countries where IBD was once considered rare (Thia 2008)...
...Oikonen 2003 examined the relationship between ambient air quality and the occurrence of multiple sclerosis relapses and found that the odds of relapse were 4-fold higher during months with the highest quartile of airborne PM. The authors concluded that poor ambient air quality may increase susceptibility to transmissible infections or enhance already existing peripheral inflammation, triggering a disease flare. Thus, it is possible that there exists a similar systemic inflammatory response to air pollution exposure that may play a role in triggering IBD flares and consequently IBD-related hospitalizations...
...county-level criteria air pollutant emissions directly correlated with the rate of IBD hospitalizations in Wisconsin...while the correlation between air pollution density and IBD hospitalizations was significant, the strength of the correlation was only moderate..."

MUTLU 2011:
"...Many of the adverse health consequences of particulate matter (PM) are thought to be caused by the ability of PM to induce cellular oxidative stress, which activates signalling pathways that contribute to cytokine release and barrier dysfunction (Nel 2005)...
...the total dose of PM to which the gut is exposed is likely at least as large as that seen by the lung. However, the more rapid transit time of the mucous layer over the gut compared with the lung mucosa may decrease the concentration of PM to which the gut is exposed at any given time..."

KAPLAN 2009:
"...A pro-inflammatory response occurs with appendicitis that includes expression of cytokines...
...Animals fed diesel particles experienced oxidative damage in colonic mucosa (Dybdal 2003)...and exposure to air pollutants, either through inhalation or ingestion, may induce inflammatory responses that are also evident in appendicitis. Alternatively, exposure to diesel exhaust has been shown to increase susceptibility to bacterial (Siguad 2007) and viral (Ciencewicki 2007) pulmonary infections through impairment of microbrial defense (Gowdy 2008). If air pollution effects gastrointestinal immunity, exposure to pollutants may increase the risk of bacterial invasion resulting in appendicitis...
...Our findings indicate that some cases of appendicitis may be triggered by short term exposure to air pollution...the effect size of the risk estimates were modest..."

BLOCK 2012:
"...It is known that PM particulates that are too large to enter the lungs are quickly cleared by swallowing (Mutlu 2011). Likewise, clearance of particles that deposit in the deep lung eventually occurs via the mucociliary escalator and so, gastrointestinal tract exposure cannot be discounted. The sensory afferents of the dorsal vagus nerve located in the gut communicate directly with brainstem neurons. It is interesting to note that abnormalities in olfaction-vagal-brainstem routes (gastric systems secondary to swallowing of nasal secretions in saliva) have been studied as the early pathologies of Parkinson's neurodegeneration (Jang 2009, Hawkes 2007)..."

EMCH 2000:

"...it is likely TNF alpha inhibits gastric motility by directly affecting the sensitivity of gastric vagal control circuitry in the medulla. This vago-vagal reflex circuit is outside the blood brain barrier and therefore is readily accessible to large circulating peptides. Additionally TNF alpha increases vascular-brain permeability and TNF alpha may gain access to the brain through a specific transport system..."

This inhibition of gastric motility or stasis is perceived as queasiness or nausea.

GI total PM dose may be large as that of the lung, however the more rapid transit time of intestinal mucosa and the potential diluting and ameliorating effects of dietary substrate may decrease exposure of the GI epithelial layer

(Mutlu 2011, Priebe 2010, Malik 2007, Prior 2003, Slavin 2003, Drewnowski 2000, Olson 1995, Groff 1990, Cummings 1987, Chako 1969, Cook 1969).

Significant associations - though modest - have been found between ambient combustion aerosol (ACA) exposure and hospitalizations for inflammatory bowel disease (Ananthakrishnan 2011) and appendicitis (Kaplan 2009).

Exposure to urban PM at doses at least 6-8 times higher than environmentally relevant are demonstrated to cause oxidant-dependent GI epithelial cell death, disruption of tight junction proteins, inflammation, and increased gut permeability; in vitro and in vivo (Mutlu 2011).

Taken together, it appears that GI symptoms are more likely to result from PM exposure when combined with a low fiber diet slowing transit time and leaving little large intestinal (colonic) substrate for bulk, dilution, and potential metabolic detoxification activity of bacterial flora.

Gastrointestinal involvement in MCS and ME/CFS, such as gastric stasis and nausea, is possibly due to communication of brain stem neurons with sensory afferents of the vagus nerve in the GI tract in response to systemic inflammatory mediators or direct PM exposure - viscero sensory pathways originating in the nucleus of the solitary tract and ventrolateral medulla - gastric vagal control circuitry (Block 2012, Calderon-Garciduenas 2008, Emch 2000).