This Transfusion: Parachutes and death from gravitational challenge | Hawthorn and heart disease | Blood group A and ovarian hyperstimulation syndrome | Rh blood group and hearing loss | Epigenetics, diet and super oxide dismutase (SOD)
Welcome to The Weekly Transfusion, 1.5 for the week of April 13, 2009.
Insufficient evidence for parachute use to prevent death and major trauma related to gravitational challenge
As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
Evidence based medicine is the buzz-phrase of the moment, the idea being that you scour the medical literature on a particular association,for example using the herb Hawthorn to treat chronic heart failure. You set the selection criteria, such as the type of study (placebo controlled, etc.) and the amalgamate the data. Evidence Basis has some very important advantages, namely that it gives the most accurate current assessment of a treatment or strategy since you are pooling all the available data.
One problem with evidence based medicine is the simple reality that evidence and benefit are not always the same thing. As shown by this slightly tongue in cheek study, there is still an insufficient evidence basis to conclude that parachutes are effective in preventing major trauma related to gravitational challenge. The researchers failed to find suitable studies showing the effects of using a parachute during free fall, despite setting logical criteria (death or major trauma, defined as an injury severity score > 15) and scouring he available literature.
Setting artificial standards can also impeded the workings of common sense: Edward Murphy put it best in his classic The Logic of Medicine: 'Only a fool would require a double-blind study to see if it was raining outside.'
Lack of evidence is not evidence of lack.
Evidence based medicine has potential to revolutionize day to day health care. However I think an even bigger revolution lurks under the surface: The reinterpretation and reorganization of medical facts derived under the older 'disease-care paradigm' by evolving paradigms that better fit new real-world circumstances.
A common argument against the need for heterodoxy in medicine is that 'when facts are proven, they stop being alternative.' This may well be true, but it neglects that facts themselves are forever open to reevaluation, deconstruction and recycling. Much of my work with the ABO polymorphisms was the simple reappraisal and restructuring of the conventional biomedical literature on the subject --but done with an eye to its ulterior benefits in naturopathic circumstances. Had they not been subjected to the 'naturopathic lens' these facts may well still be floating in their own splendid isolation.
Hawthorn extract for treating chronic heart failure
For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo... Exercise tolerance were significantly increased by hawthorn extract... The pressure-heart rate product, an index of cardiac oxygen consumption, also showed a beneficial decrease with hawthorn treatment... Symptoms such as shortness of breath and fatigue improved significantly with hawthorn treatment as compared with placebo...These results suggest that there is a significant benefit in symptom control and physiologic outcomes from hawthorn extract as an adjunctive treatment for chronic heart failure.
I first wrote about Hawthorn (Crataegus spp.) in my book Eat Right For Your Type over thirteen years ago, making specific reference to its benefit for blood group A individuals with cardiovascular problems. In general the plant has a good track record, especially, if used in quite low doses for extended periods of time. The herb seems to allow cardiac patients to derive extra benefit from exercise (link), has some very nice effects on the artery lining (link) and has been shown to lower blood pressure in patients taking diabetic medication. (link)
Hawthorn was shown to be well tolerated and safe. However, it should not be used as a substitute medication in circumstances of active heart disease or concurrently with other cardiac medicines unless under the supervision of a physician trained in its use. In one study, it actually seemed that the hawthorn group had a worse outcome than the placebo group. (link) Hawthorn also does produce occasional side-effects, though they appear uncommon and rather mild.(link) Perhaps this is the darker side of the biochemical individuality revolution; it's no longer acceptable to claim that all natural products are safe in every person. Anything that can add to the personalization of herbal recommendations can only help to increase their safety profile.
Blood type A women get more complications from fertility treatment
Ovarian hyperstimulation syndrome is a potentially life-threatening complication during controlled ovarian stimulation for fertility treatment. Since no association of this condition with ABO blood groups was known, we compared ABO antigens with severity and onset of symptoms in a case-control study...The odds ratio for patients undergoing controlled ovarian stimulation with blood group A versus O to develop the early-onset form of this condition was 2.171 (p-value 0.002). Blood group A may be associated with early-onset ovarian hyper-stimulation syndrome in Caucasians...This possible association may be considered for an individualized hormone dosing in controlled ovarian stimulation.
Ovarian hyperstimulation syndrome (OHSS) is a complication from some forms of fertility medication. Most cases are mild, but a small proportion is severe. Symptoms can range from a more mild form that includes abdominal bloating and feeling of fullness, nausea, diarrhea, and slight weight gain to a more severe form that includes and fullness/bloating above the waist, shortness of breath, urination significantly darker or cessation of urination altogether, calf and chest pains, marked abdominal bloating or distention, and lower abdominal pains. This study looked at 127 Caucasian patients hospitalized because of ovarian hyperstimulation syndrome after receiving in vitro fertilization, in the period from January 2000 to February 2007 and found that blood group A was markedly more frequent and blood group O less frequent in patients with ovarian hyperstimulation syndrome.
Other studies have found a slightly greater incidence of ovarian cancer in women who are blood group A (link) and blood group antigens (as mucins or 'blood group substances') are known to be richly deposited on ovarian tissue. (link) Hopefully fertility specialists will consider individualizing hormonal treatment by blood group when working with fertility patients.
Four patients developed thrombosis (clots) in the jugular or subclavian vein, none of whom had blood group O; this correlates with earlier studies linking blood groups other that type O with an increased risk of thrombosis (link) at some of this clotting may in fact be due to enhanced sensitivity to estrogen, at least in women who are not blood group O.(link)
What was that? Being Rh positive may increase your risk of hearing loss
Noise-induced hearing loss (NIHL) is one of the most common occupational problems and is one of the main causes of deafness. Many factors cause NIHL. Individual susceptibility is one of them. Rhesus (Rh) antigens and ABO blood groups can be factors in determining individual susceptibility. In conclusion, we suggest that the people with Rh-positive blood group are more prone to develop NIHL.
The researchers looked at factory workers who had been exposed to a noise level more than 85 dB for 8 hours a day for a period of over 15 years. Two hundred and nineteen (55.4%) of Rh-positive workers and seventeen (39.5%) of Rh-negative workers have noise-induced hearing loss, and the difference between the two groups was statistically significant (P < 0.05). There was no link between hearing loss and ABO blood type.
If you are a rabid reader of this blog, you'd immediately notice that these results are just ever-so-slightly statistically significant (and not be much of a discovery) since given enough noise, virtually anyone will develop hearing loss. However we could speculate that something in being Rh positive influences the structure of the ear anatomy to make these people more likely to get hearing damage. Or on the other hand, what is it about being Rh negative that makes these people less likely to get hearing loss?
An earlier study with infants and adults also showed a higher incidence of hearing loss in Rh positive people, with a slightly better level of significance (0.01) if the mother was Rh negative blood type (which might support the idea that the problem would then be seen in the incompatible Rh-positive children). Another maternal influence via blood group!
Diet influences epigenetic regulation of super oxide dismutase (SOD) gene
The impact of nutrition on the epigenetic machinery has increasingly attracted interest. The aim of the present study was to demonstrate the effects of various diets on methylation and gene expression. The antioxidative enzyme mitochondrial superoxide dismutase (MnSOD) was chosen as the model system because epigenetic regulation has been previously shown in cell lines for this gene. A 3-fold increase in the expression of the MnSOD gene was associated with decreased CpG methylation of the analyzed promoter region in the vegetarian group compared with the age-matched omnivores group. These results indicate that diet affects the epigenetic regulation of human MnSOD.
The super oxide dismutases are a class of enzymes that catalyze the conversion of free radical superoxide molecules into oxygen and hydrogen peroxide. They are an important antioxidant defense in nearly all cells exposed to oxygen. SODs 'outcompete' healthy tissue for the damaging free radical molecules. They protect the cell in a way reminiscent of a common scene in the the old Laurel and Hardy movies where two soldiers in a trench hoist a helmet on a stick above their heads and then retrieve it having been shot full of bullet holes. Although SOD supplements are a common item on health food store shelves, oral SOD products are completely destroyed in the gut, so methods to increase the native (endogenous) production in our own cells would be optimal.
Epigenetics is best explained as the 'non-genomic' or 'post-genomic' control of gene expression, mechanisms such as DNA methylation, or histone acetylation, which act a 'volume controls' on the ability of the cell to read the section of DNA that contains that gene. In the case of this study, the vegetarian group has less methylation on the CpG section of promoter region of the SOD gene.
In English, what they are saying is that diet removed some of the restrictions (methyl groups) on the part of the gene that activates it (the promoter region). Removing methyl groups usually takes the brakes off a gene, especially when they are in the gene's cystine-rich 'front.'
Exciting stuff. Now we'll need to see exactly which specific foods have the maximum epigenetic effects on SOD.
Until next week.
Note to readers: By mistake I had uploaded an earlier, non-spell-checked version of this entry on Monday. I beg your indulgence on this matter. Although I am a reasonably good speller, if truth be told I am a terrible typist.
Welcome to The Weekly Transfusion, 1.4 for the week of April 6, 2009.
Editorial: Medical journal statistics for autodidacts
You can become a better consumer of health information if you take the time to read the research source material (i.e the scientific publication in which the original claim was made). Of course if the study is technical you can see quite a bit of jargon that you may or may not understand. However many medical terms are widely understood and where you bump up against the odd phrase or name that you don't comprehend, there are usually places on the Internet where you can find simple, easy to understand explanations. Wikipedia is actually pretty good for this type of look-up, as long as the subject at hand is not controversial.
However, methodology and monikers aside, most scientific studies distill down to a simple testable premise which is easily understand by almost anyone. Did the medicine work? Was the association between this gene and that disease valid? Past asking the question, what is needed next is to look at and gauge the value of the answer. Surprisingly, even though this is usually some sort of statistical type of answer (and most laypeople are not well versed in statistics) once you know what to look for, you'd be amazed just how easy it is to evaluate most studies.
Most research studies feature a subsection entitled Results or Conclusions. It is here that the results are most often given. There are many way of calculating statistical significance, but the premise is quite simple: What is the chance that the thing we just observed/ hypothesized was random versus the odds of it being due to the relationship we are studying. This is known as probability and in statistics is usually called the P value. To find out just how significant the results of any study are, just look for the P value. The smaller this number is, the less likely the results occurred by chance. Put another way, the lower the P value the more likely you'll want to view the results as significant or important.
The great Ronald Fisher viewed P values as measures of the evidence against a hypotheses, sort of like how a prosecutor presents a case based on exceeding the jury's sense of 'reasonable doubt.'
Now for the secret (OK, not so secret) key to taking control of the medical facts in your life: The standard level of significance used to justify a claim of a statistically significant effect is when P is equal to or less than 0.05; in essence, a one-in-twenty chance that the result had nothing to do with your hypothesis.
For better or worse, the term 'statistically significant' has become synonymous with P<=0.05.
So when looking at any published results, always look for the P value and if it is greater than five cents on the dollar (0.05) you'd probably want to ignore that results (unless the premise of the article was that the researchers failed to show a relationship, which is of course just another type of observation; however, these types of studies usually don't make it out of the researcher's file cabinet) or take a look at the methodology behind the study (scientists are human; studies can be poorly designed and the conclusions derived may not have been the best test of the hypothesis).
So, P<0.05 means the results are significant, but just barely. Good enough to convict, but also likely to send a few innocent people to jail as well, since there are still strong indications that the hypothesis fails to account for the whole of the facts. Personally I like to see P values of at most 0.01-0.02 before I get excited about anything I'm reading. However I do make exceptions for studies with small numbers of participants, or if the we're dealing with an herb or vitamin where the effects studies may be slight or slow to surface.
Oftentimes you'll see P values with lots of zeros. That means they've found a more statistically reliable result. For example, the P value in the following article is P<0.001. This actually means that there 1 in a 1000 chance of the result being a random occurrence and a 999 in 1000 chance that the result was related to the premise of the study.
Just remember, look for at least a P<0.05. That means the results were statistically significant. Beyond that the more zeros you see in the P value, the better. Try your new-found statistical powers on the articles below. Look for the P values in the studies. What do they signify?
Now that you can evaluate scientific material at its source, you'll be less likely to fall for the 'man bites dog' con-jobs that are all too commonly reported in the news or as what passes for scientific discussion these days.
Resting heart rate as a low tech predictor of heart problems in women
In a large, diverse group of postmenopausal women, resting heart rate was an independent predictor of coronary events, with higher heart rate associated with greater risk. The relation between resting heart rate and risk of coronary events was stronger in younger postmenopausal women than in older ones. Resting heart rate did not independently predict stroke.
In general, age, body mass index, and saturated fat consumption were higher and cardiovascular risk factors such as hypertension, diabetes, smoking, hypercholesterolaemia, and depressive symptoms more prevalent in women with higher resting heart rate, as was self reported nervousness. Physical activity and alcohol use were inversely related to heart rate (both P<0.001), and heart rate was lower in women who used postmenopausal hormone therapy than in those who did not (P<0.001).
One can't argue that this is about as low tech a predictor of future health problems as one is likely to find. It has already been shown that resting heart rate predicts coronary events in men. For women however, the relation between heart rate and coronary events or stroke has been uncertain. The study broke the participants into groups including a 'high heart rate group' whose heart rate was greater that 76 beats per minute and 'low heart rate group' whose heart rate was greater than 61 beats per minute. The association with 'coronary events' (aka heart attacks and death). This association appears stronger in women aged 50-64 than in those aged 65 or older
Being overweight makes you age faster
Obesity and weight gain in adulthood are associated with an increased risk of several cancers. Telomeres play a critical role in maintaining genomic integrity and may be involved in carcinogenesis. Using data from 647 women ages 35 to 74 years in the United States and Puerto Rico (2003-2004), we examined the association between current and past anthropometric characteristics and telomere length in blood. These findings support the hypothesis that obesity may accelerate aging, and highlight the importance of maintaining a desirable weight in adulthood.
A telomere is a region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction. When DNA needs to be read (to replicate itself, or generate RNA so as to begin coding proteins) a problem arises in that the enzymes that duplicate the chromosome and its DNA cannot continue their duplication all the way to the end of the chromosome. They need a blank area to 'park' much like the cassette tapes of days past had white 'leader tape' at their front and the back so that the tape head did not start in the song itself. Unlike cassette tape, every time DNA reproduces, a bit of the white leader tape, the 'telomere' at the end, is frittered off and has to be replaced. Telomeres and replenished by an enzyme, the telomerase reverse transcriptase. Telomeres protect a cell's chromosomes from fusing with each other or rearranging - abnormalities which can lead to cancer - and so cells are normally destroyed when their telomeres are consumed. In the women studies for this article, those having a higher body mass index (BMI) in their 30s were associated with shorter telomere length in their 40s (P < 0.01).
I suspect some of this association is epigenetic, and points again to the fact that the GT5 Warrior epigenotype may well need to get their weight profile optimized early in life and be increasingly calorie conscious as they age.
Vitamin D, adult-onset diabetes and metabolic syndrome
Vitamin D is a potent immunomodulator that also enhances the production and secretion of several hormones, including insulin. Vitamin D deficiency has been associated with increased risk of type 1 diabetes. Glycemic control and insulin resistance are improved when vitamin D deficiency is corrected and calcium supplementation is adequate.
More and more information is surfacing about vitamin D (actually more of a hormone than a vitamin) and insulin resistance. Studies consistently show that vitamin D levels in both North America and the Pacific are typically lower than optimal. In the USA , most vitamin D intake from foods is provided by fortification. Canada and New Zealand have fewer fortified choices, and intakes are correspondingly lower. The mechanism of action of vitamin D in adult onset (type 2) diabetes is thought to be to its role in the control of plasma calcium levels, which help regulate insulin synthesis, but may also be the result of vitamin D stimulating the insulin secreting (beta) cells of the pancreas directly. If you have a history of metabolic syndrome or adult onset diabetes in close family members you may want to consider adding vitamin D to your supplement regimen. However, make sure that you do it in partnership with a nutrition professional.
One from the vaults: Mom's blood type can influence child's risk of Strep (1978)
In a prospective study of maternal genital colonization with streptococci at the time of delivery, epidemiological data, including blood type (ABO group), were recorded for the 1,062 patients studied. Blood type B was found in a statistically significant (P <.005) higher proportion of patients colonized with streptococci (28%) compared with the total population (16.4%)
Evidence suggests that probiotic supplementation does change the vagina flora of women. Since it appears that the route of transmission of Streptococcus is from the birth canal, physicians should recommend probiotic supplementation for pregnant women beginning 3-4 weeks prior to expected date of delivery as a way to prevent streptococcus infection in neonates. This should be especially emphasized if the mother is either blood group B or AB.
This study again illustrates the fact that some of the best ABO correlation studies are outside the purview to today's physicians, most of whom would tell you that any research from 1978 is better suited to a history class than to any thing taught in medical school.
Since Mother's Day is fast approaching, also remember that recurring otitis media (ear infections) is strongly associated with the child's mother being blood type A. In fact the correlation here is quite startling. Children of mothers who are blood type A are twenty seven times more likely to get a second ear infection within one year of contracting the first. To give you an idea of just how strong this association is, look at the chart below to compare the RR (relative risks) of a few other disease/ lifestyle links.
Update: IfHI 2009
Just a quick word to the wise about the IfHI Conference, Norwalk Connecticut, June 5-7. We had run out of available rooms at the Dolce Center Campus. However 10 additional rooms have just been made available. Unlike previous conferences, where attendees could book almost to the day of the event, IfHI 2009 looks like it will be completely booked by the middle of May, a full month before the event. If you are planning on attending, either for certification or just personal enrichment, please make your reservations ASAP, especially if you want to stay overnight on campus.
Until next week.
From Percept Mot Skills. 2008 Dec;107(3):737-46.
Twin and family study findings indicate a substantial heritability of digit ratio (2D:4D), a putative marker for the masculinizing effects of prenatal androgen exposure. Functional polymorphisms of the X-linked androgen receptor gene, i.e., androgen sensitivity, contribute somewhat to the expression of 2D:4D in men, but otherwise the genetics of 2D:4D is unknown. This study investigated differences in 2D:4D by self-reported ABO blood type and Rhesus factor, two easily collectible genetic traits, in two samples (combined N=1273). Effects of blood groups on 2D:4D were small and not significant in all tests in both samples; however, two consistent patterns emerged across samples. Of the ABO types, AB had the lowest right-hand 2D:4D, the highest left-hand 2D:4D, and the lowest right-minus-left difference in 2D:4D, and Rhesus factor Rh- had higher left-hand 2D:4D and lower right-minus-left difference in 2D:4D than Rh+. If replicable, this may suggest genes contributing to the expression of 2D:4D reside in the vicinity of the gene loci (chromosomal locations: 9q34.2 and 1p36.11) of these blood groups or pleiotropic effects of the blood-group genes.
As if I needed further convinced that epigenetics (the control of gene expression through nutrition) is the great wave of the future, a pre-publication results of a study released to members of The Epigenetic Society should satisfy for quite a while.
In a study soon to be published in the Journal Biological Psychiatry, researchers looked at the epigenetic effects of childhood maltreatment and early trauma. Using laboratory rats (whose epigenetic mechanisms are very similar to humans) the researchers exposed infant rats to stressed caretakers who predominately displayed abusive behaviors.
They found that early maltreatment produced persistent changes in the methylation of a gene called BDNF (brain derived neurotrophic factor) that is responsible for the developmental health of the cerebral cortex.
In addition, they observed disturbed BDNF methylation in the offspring of females that had previously experienced the maltreatment regimen, indicating that the epigenetic effects of abuse, trauma and neglect were carried from one generation to the next.
The GenoType Diet carries the promise of a genetic redemption of sorts, since as in the words of one researcher “Unlike defective genes, which are damaged for life, methylated genes can be demethylated. And, methyl tags that are knocked off can be regained via nutrients, drugs, and enriching experiences.” (2)
- Tania L. Roth TL, Farah D. Lubin FD, Adam J. Funk and J. David Sweatt. Lasting Epigenetic Influence of Early-life Adversity on the BDNF Gene. Biological Psychiatry, In Press
- Asim K. Duttaroy Evolution, Epigenetics, and Maternal Nutrition 2006 Darwin Day Celebration.
The New York Times had an extensive discussion of epigenetics in their February 24 issue:
The ideal of regenerative medicine is to convert a patient’s normal body cells first back into the embryonic state, and then into the specific cells lost to disease. But to prepare such cells safely and effectively, researchers will probably need to learn how to control and manipulate the chromatin of the epigenome as well as the transcription factors that shape cell identity.