13.5.12

Raw Milk Wipes Away the Wheeze: How Our Good Friend Glutathione Protects Against Asthma | Mother Nature Obeyed - Weston A Price Foundation

With the Wave of a Wand, Raw Milk Wipes Away the Wheeze: How Our Good Friend Glutathione Protects Against Asthma | Mother Nature Obeyed - Weston A Price Foundation

Our valiant, cape-wearing, free radical-wrestling, toxicant-thwarting Raw Milk is back in town with his courageous army of raw food volunteers, and this time their mission is to get our good friend glutathione back in the bronchioles where this talented little tripeptide will make all things new, wiping away the wheeze and taking the anguish out of the asthma.

Children Who Drink Raw Milk Are Less Likely to Have Asthma

In October of last year, the investigators of the GABRIELA study published an analysis in the Journal of Allergy and Clinical Immunology showing that children who drink raw milk are less likely to have asthma (1).  The investigators surveyed the parents of almost 35,000 children between the ages of six and twelve living in rural areas of Germany, Switzerland, and Austria to determine how likely they were to live on a farm or to have exposure to farms in some other way.  They then selected a random sample of this population with similar rates of farm exposure, sending a much more detailed questionnaire to the parents of over 8,000 children, taking blood samples from over 7,500, and even taking samples of milk from the homes of 800.

The investigators reported the data after adjusting for farm status, specific location, age, sex, breastfeeding, family size, and the presence of asthma in the family tree.  The results were impressive.  Compared to children who drank only pasteurized milk from the local shop, children who drank raw milk from the local farm on a less than daily basis were forty percent less likely to have asthma while kids who reveled in this rawness on the daily were half as likely to be wrestling with the wheeze.

But wait, was it really the rawness that delivered them?  Correlation is never causation no matter how cool the correlation can be, so we can’t attribute any saving grace to the creamy white stuff just yet.  But there’s one thing we can say for sure: take out the rawness, and the correlation goes kaput.  Children who drank only boiled milk from the farm were 60 percent more likely to have asthma as those who drank only pasteurized milk from the shop, but because there were only a sixth as many of these kids, the association just barely slithered under the statistical radar.

Lower risk of asthma with raw milk. 
Is there a nugget of causation lying somewhere deep within the heart of this correlation?  If so, is it a nugget of sheer nastiness revealing nothing beautiful but only the hidden dangers of heat treatment, or is it a pearl of great price revealing the protective powers of unpasteurized goodness?  We can get a glimpse of the likely explanation by putting on our “analytical chemistry” hats and peering into a few of the 800 glasses of milk the investigators collected from the homes of the study participants.  Only through deep meditation and the assistance of modern laboratory equipment does the visible world begin to fade from our sight and the glory of our good friend glutathione come to light.

The Raw Whey Proteins Are Where It’s At

As we peer into these molecular mysteries in all their lactational luster, we should keep in mind that the shop milk and farm milk come from different sources, so differences in the data reflect more than the simple effect of heat treatment.*  That caveat aside, let’s take a look.
The investigators divided the shop milk into two cateogories: milk that had only been heated to the minimum standards for pasteurization, and milk that had been heated with higher temperatures, for which I’ll use the term “ultra-high temperature (UHT) treatment” throughout the rest of this post.** Over 90 percent of the shop milk was UHT-treated, so this is the most important milk to look at when trying to solve the riddle of how rawness may have reduced the risk of asthma.


We’ll start with the obvious stuff.  Surprise!  Raw milk had more bacteria.

 
A lot more!  And believe it or not, that “c” above the invisible UHT bar means there’s even less bacteria in UHT milk than in the boiled and pasteurized milks and it’s statistically significant to boot!

Now let’s look at transforming growth factor beta-2, a protein that is believed to suppress inappropriate immune responses.  Raw milk was almost twice as high as UHT milk and almost four times as high as boiled milk, although the minimally pasteurized milk from the shop had the most.

 
Moving on, we come to lactoferrin, a protein that inhibits the growth of pathogenic bacteria, encourages the growth of probiotic bacteria, acts as an antioxidant, and helps our intestinal cells make their own lactase, the enzyme that digests lactose.

 
No, I didn’t forget to draw the bars for the boiled and UHT milks.  Both of these treatments obliterate lactoferrin.  In fact, the raw milk was a whopping 2,866 times higher in lactoferrin than boiled milk and a mind-blowing 8,026 times higher than UHT milk!  Minimal pasteurization caused a lesser loss of lactoferrin: raw milk was 36 percent higher, but the difference was not statistically significant.

Got antibodies?

 
Not if you’ve been pasteurized.

Whether cow antibodies play functional roles in humans is unclear, but, if they do, those roles must be altered or lost upon pasteurization.***

And now we come to the milky, creamy part where things start to get whey cool.  In “The Biochemical Magic of Raw Milk and Other Raw Foods: Glutathione,” I provided evidence that pasteurization not only lowers the total whey content of milk, but also selectively destroys bovine serum albumin and beta-lactoglobulin so that the remaining whey contains a lower proportion of these two proteins than it otherwise would.  Throughout the food supply, only these whey proteins and the ovomucoid protein in egg white possess unique glutathione-boosting glutamyl-cysteine bonds (2).

 
Raw milk had 56 percent more bovine serum albumin (BSA) than pasteurized milk.  For boiled and UHT milk, well, you know the drill.  These treatments obliterated the BSA.

 
Minimally pasteurized milk fared better for beta-lactoglobulin than for BSA.  It had only eight percent less of this protein than raw milk and the difference was not statistically significant.  This conflicts with research I cited in “Biochemical Magic” showing that HTST pasteurized milk has thirty percent less total whey protein than raw milk (3), and that the remaining whey protein itself has 22 percent less beta-lactoglobulin (4), suggesting an overall 45 percent loss of this protein.  UHT treatment and boiling nevertheless blew beta-lactoglobulin into oblivion, causing losses of about 85-95 percent, and these are the treatments most relevant to the riddle of asthma we are seeking to solve.

 
Alpha-lactalbumin is the other major whey protein, but it doesn’t contain any glutathione-boosting glutamyl-cysteine bonds.  It appears to survive minimal pasteurization quite well, although boiled and UHT milks had about 70 percent less than raw milk.****  Since alpha-lactalbumin lacks the special glutathione-boosting bonds possessed by BSA and beta-lactoglobulin, its greater heat-stability suggested by this study is consistent with the research I cited in “Biochemical Magic” showing that heat treatment not only depletes the total whey protein content of milk, but also renders the remaining whey protein less capable of boosting glutathione status.

Statistically, kids who drank the milk richest in the major whey proteins had the lowest risk of asthma. None of the other milk components measured had statistically significant relationships with asthma risk.  Lack of correlation doesn’t necessarily mean lack of causation, so we shouldn’t take this finding to mean that probiotic bacteria, IgG antibodies, lactoferrin, and TGF-β2 offer no protection.  We should, however, begin to wonder whether our good friend glutathione might be lurking behind a powerful protection offered by raw milk whey proteins.

How Our Good Friend Glutathione Protects Against Asthma

Serendipitously, while the GABRIELA investigators were studying the relationship between raw milk and asthma, researchers from the Emory University Departments of Medicine and Pediatrics and the Children’s Health Care of Atlanta Center for Developmental Lung Biology were preparing a massive 102-page tome reviewing the relationship between glutathione and asthma.  They published it this March in the journal Antioxidants and Redox Signaling (5).
Glutathione plays four major roles within the body:
  • Safe storage of the highly vulnerable and potentially toxic amino acid cysteine.
  • Protection against oxidative stress.
  • Detoxification.
  • Cellular communication and regulation of protein function.
Glutathione is generally present in the highest concentrations inside cells rather than outside.  Indeed, most cells contain between a hundred and a thousand times more glutathione than is present in our blood.  The extracellular fluid of the lungs, by contrast, is an exception to the rule.  Glutathione concentrations there are a hundred times higher than in our blood, rivaling the concentrations within many cells.  These high glutathione concentrations in lung fluid appear to have at least two special roles:
  • A high concentration of glutathione is necessary to maintain the fluidity of mucus.
  • Glutathione combines with another chemical called nitric oxide to produce nitrosoglutathione.
Nitric oxide is glutathione’s jet pack.  When this G gets his nitrous on, he becomes a bronchodilator 100 times more supercharged than theophylline, a once-common asthma drug that has largely been abandoned because of its side effects.  This means that nitrosoglutathione decreases resistance in the airway and increases the flow of air to the lungs — exactly what asthma drugs are designed to do!  In fact, nitrosoglutathione dilates the bronchioles by stimulating the same receptors as albuterol, a common asthma drug (6).  Inhaled corticosteroids synergize with albuterol by increasing the production of these receptors (7).

Could asthma largely result from a deficiency of glutathione and nitrosoglutathione in the extracellular fluid of the lungs?  Data presented in the recent review would suggest so (5).  Among the most compelling of these data we find two startling facts:
  • Children with severe asthma have three times less glutathione in their lung fluid than healthy adults and two times less than children with moderate asthma, while they have two to four times as much oxidized glutathione.  They also have 30 percent less cysteine in their blood, suggesting that they may not have enough cysteine to keep producing the glutathione they need.
  • Asthmatics have 70 to 90 percent less nitrosoglutathione in their lung fluid as healthy controls, and nitrosoglutathione becomes undetectable during severe asthma attacks.
Scientists are currently focusing on the role of an enzyme that destroys nitrosoglutathione.  The activity of this enzyme is increased in asthma, and researchers are currently studying whether genetic variations or inflammatory insults are responsible for this increase.  Test tube studies, however, suggest that glutathione itself suppresses the activity of this enzyme (8).  Thus, the more glutathione we have, the more nitrosoglutathione we should have.

It may be the case, then, that asthma results largely from a deficiency of glutathione in the lung fluid while common asthma drugs like corticosteroids and albuterol are simply band-aid solutions aimed at replacing the natural effects of glutathione with cheap imitations.



Help Our Hero Save the Day!

There’s no better way we could help Raw Milk and his courageous army of raw food volunteers in their quest to abolish asthma than to do what any conscientious bystander would do when a panoply of edible superheroes parades through town: put them in our mouths.  There are a number of other factors, however, that could help maintain robust glutathione status:
  • Eat enough protein, which supports glutathione synthesis and recycling.
  • Take in enough thiamin, niacin, riboflavin, vitamin B6, and magnesium, which support glutathione synthesis and recycling.
  • Maintain a high metabolic rate, which supports glutathione synthesis and recycling.
  • Consume collagen-rich animal parts and bone broth to obtain extra glycine, which is needed for glutathione synthesis and depleted in asthma patients.
  • Maintain an adequate intake of selenium, which helps glutathione protect against oxidative stress.
  • Maintain adequate intakes of vitamins C and E, iron, copper, zinc, and manganese, which contribute to the antioxidant defense system and thereby help spare glutathione.
  • Consume plenty of unrefined foods, especially fresh, raw fruits and vegetables.  The polyphenols present in unrefined foods boost glutathione synthesis through hormesis, and raw fruits and vegetables contain large amounts of preformed dietary glutathione.
Glutathione, moreover, is unlikely to be the be-all, end-all of asthma.  In my article on vitamin D in infant nutrition, for example, I outlined evidence suggesting vitamin A deficiency is also involved.

The scientist in me hopes to see randomized, controlled trials comparing the ability of raw milk, pasteurized milk, UHT-treated milk, and milk-free diets to prevent and treat asthma, and comparing their effects with and without other nutritional treatments, such as the inclusion of liver, bone broth, and other nutrient-dense foods, and dietary or lifestyle interventions aimed at increasing the metabolic rate.  In the mean time, self-experimentation using any of these approaches just might bring a breath of fresh air where it is most needed.

Notes

*  We should also keep in mind that all of the proteins discussed herein were measured by antibody-based assays, and so I’ve called this “analytical chemistry” in part out of poetic license and in part out of generosity towards the researchers.  The tests aren’t really measuring how much of a specific protein is there, but rather how much will bind to the antibodies they purchased.  If there is a difference between milks, it shows that heat has somehow altered or destroyed the protein, but it doesn’t tell us which of these occurred, and it doesn’t tell us what the true effect of heat treatment would be on the biological activity of the protein.  For the purpose of simplicity, however, I have reported the data as if they were measuring the presence of the protein.

**  The investigators measured two enzymes in the milk to determine how much heat treatment it had endured.  If they found major destruction of alkaline phosphatase but only modest destruction of lactoperoxidase, they considered the milk to have been pasteurized using the high-temperature, short-time (HTST) method, which heats the milk to 72 degrees Celsius for 15 seconds.  If they found major destruction of lactoperoxidase, they called it “high heat-treated,” which means the milk was brought to at least 85 degrees Celsius for at least 5 seconds, although lactoperoxidase destruction is also a feature of ultra-high temperature (UHT) treatment, which brings the milk to about 140 degrees Celsius for just a second or two.  For the sake of simplicity, I have used the terms “pasteurized” and “ultra-high temperature-treated” (UHT) to describe these two treatments, but in reality the exact method used to treat each sample is unknown.

***  Reference 2 lists the glutamyl-cysteine content of IgG as unknown.  Unless this has been subsequently determined, it may remain a possibility that bovine IgG contributes to the glutathione-boosting properties of raw milk along with BSA and beta-lactoglobulin.

**** As indicated by the “a” above the bar for boiled milk, the 70 percent lower alpha-lactalbumin content of boiled milk was not statistically significant.  This is because of enormous variation among the different samples of boiled milk.

References

1.  Loss G, et al. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study. J Allergy Clin Immunol. 2011;128(4):766-73.
2.  Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med. 1991;14(4):296-309.
3.  Carbonaro M, Cappelloni M, Sabbadini S, Carnovale E. Disulfide Reactivity and In Vitro Protein Digestibility of Different Thermal-Treated Milk Samples and Whey Proteins. J Agric Food Chem. 1997;45(1):95-100.
4.  Morales FJ, Romero C, Jimenez-Perez S. Characterization of industrial processed milk by analysis of heat-induced changes. Int J Food Sci Tech. 2000;35(2):193-200.
5.  Fitzpatrick AM, Jones DP, Brown LA. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid Redox Signal. 2012; Mar 9 [Epub ahead of print]
6.  Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005;308(5728):1618-21.
7.  de Benedictis FM, Bush A. Corticosteroids in respiratory diseases in children. Am J Respir Crit Care Med. 2012;185(1):12-23.
8.  Thompson CM, Sonawane B, Graftstrom RC.  The ontongeny, distribution, and regulation of alcohol dehydrogenase 3: implications for pulmonary physiology. Drug Metab Dispos. 2009;37(8):1565-71.